beta-endorphin and Alcoholism

Psychiatric pharmacogenetics involves the use of genetic tests that can predict the effectiveness of treatments for individual patients with mental illness such as drug dependence. This review aims to cover these developments in the pharmacotherapy of alcohol and opiates, two addictive drugs for which we have the majority of our FDA approved pharmacotherapies.. We conducted a literature review using Medline searching terms related to these two drugs and their pharmacotherapies crossed with related genetic studies.. Alcohol's physiological and subjective effects are associated with enhanced beta-endorphin release. Naltrexone increases baseline beta-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. Caucasians with various forms of the CYP2D6 enzyme results in a 'poor metabolizer' phenotype and appear to be protected from developing opioid dependence. Others with a "ultra-rapid metabolizer" phenotype do poorly on methadone maintenance and have frequent withdrawal symptoms. These patients can do well using buprenorphine because it is not significantly metabolized by CYP2D6.. Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic and pharmacokinetic factors. These mutations guide pharmacotherapeutic agent choice for optimum treatment of alcohol and opiate abuse and subsequent relapse.

Topics: Alcoholism; beta-Endorphin; Buprenorphine; Cytochrome P-450 CYP2D6; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Predictive Value of Tests; Receptors, Opioid, mu

Alcohol is one of the most commonly abused substances, and its chronic intake leads to the development of ethanol dependence in both humans and laboratory animals. In many countries, a mu-opioid receptor antagonist naltrexone has been used in the treatment of alcohol dependence. The introduction of naltrexone for the treatment of alcohol dependence has been mainly based on behavioral animal models that provide evidence of the involvement of the endogenous opioid system in alcohol drinking and dependence. It has been well known that alcohol leads to the activation of the endogenous opioid system. The endogenous opioid agonists, such as beta-endorphin, increase the activity of the mesolimbic dopaminergic system through the inhibition of the gamma-aminobutyric acid (GABA)-containing inhibitory interneurons in the ventral tegmental area, resulting in the expression of alcohol reinforcement and/or rewarding effect. Therefore, naltrexone, which is useful for alcohol dependence therapy, may attenuate the rewarding effect of ethanol by interfering with the ethanol-induced stimulation of the mesolimbic dopaminergic system. The following review provides a summary of the interactions between endogenous opioid system and mesolimbic dopaminergic system in alcohol dependence.

Topics: Alcoholism; Animals; beta-Endorphin; Dopamine; GABA Antagonists; Humans; Naltrexone; Narcotic Antagonists; Receptors, Opioid, mu; Reinforcement, Psychology; Reward

Human and animal studies suggest that there is a correlation between endogenous opioid peptides, especially beta-endorphin, and alcohol abuse. It has been proven that the consumption of alcohol activates the endogenous opioid system. Consumption of alcohol results in an increase in beta-endorphin level in those regions of the human brain, which are associated with a reward system. However, it has also been observed that habitual alcohol consumption leads to a beta-endorphin deficiency. It is a well-documented phenomenon that people with a genetic deficit of beta-endorphin peptide are particularly susceptible to alcoholism. The plasma level of beta-endorphin in subjects genetically at high risk of excessive alcohol consumption shows lower basal activity of this peptide. Its release increases significantly after alcohol consumption. Clinical and laboratory studies confirm that certain genetically determined factors might increase the individual's vulnerability to alcohol abuse.

Topics: Alcoholism; Animals; beta-Endorphin; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Mice; Rats

Neuropeptides have been implicated in experimental drug addiction. Desglycinamide (Arg8) vasopressin (DGAVP) attenuates heroin and cocaine intake during initiation of drug self-administration in rats. beta-Endorphin is self-administered in rats and a role of endogenous opioids in cocaine reward has been proposed. The present studies deal with voluntary alcohol consumption in monkeys under free choice conditions. Monkeys initiated alcohol drinking within a few days and after a stable drinking pattern was acquired increased their ethanol consumption during a short period following interruption of the alcohol supply (relapse). The alcohol drinking behavior seems under the control of reinforcement principles. DGAVP reduced the acquisition of alcohol drinking in the majority of treated monkeys. Initiation of alcohol drinking induced modifications in neuroendocrine homeostasis e.g. an increased plasma beta-endorphin. Both the opioid antagonist naltrexone and the opioid agonist morphine dose-dependently decreased alcohol intake during continuous supply and after imposed abstinence. The monkeys were more sensitive to both drugs after imposed abstinence. The effects are interpreted in the context of the endorphin compensation hypothesis of addictive behavior. It is suggested that endorphins may be particularly implicated in craving for addictive drugs and in relapse of addictive behavior.

Topics: Alcoholism; Animals; beta-Endorphin; Ethanol; Humans; Macaca mulatta; Male; Morphine; Naltrexone; Neuropeptides; Rats; Reinforcement, Psychology; Self Administration

Topics: Alcoholism; Angiotensin II; Animals; beta-Endorphin; Bradykinin; Brain; Enkephalins; Motivation; Oligopeptides

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Alcoholism; Animals; beta-Endorphin; Child; Disease Susceptibility; Electroencephalography; Female; Genetic Markers; Humans; Male; Mice; Mice, Inbred Strains; Prolactin

Evidence indicates that both genetic and environmental factors, such as stress, may play an important role for the development of alcoholism, while beta-endorphin may be implicated in the control of alcohol consumption. The objective of the present studies was to test the hypothesis that there are differences in the response of the pituitary beta-endorphin system to stress as a function of family history of alcoholism and alcohol dependence.. The response of the pituitary beta-endorphin to a placebo or an alcohol (0.50 g ethanol/kg) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink was measured in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, each subject participated in 4 experimental sessions given on different days in a randomized order. Four groups of subjects were investigated: 1) low risk nonalcoholics (LRNA); 2) high risk nonalcoholics (HRNA), 3) low risk alcoholics (LRA); and 4) high risk alcoholics (HRA). Plasma beta-endorphin was estimated prior to and for 3.5 hr post-stress. Changes in the concentration of plasma beta-endorphin following ingestion of either the placebo or alcohol drink without performance of the stress task served as controls to compare the stress-induced changes.. Basal plasma beta-endorphin levels were higher in LRNA than LRA, HRNA and HRA participants, while basal plasma beta-endorphin levels were higher in LRA than those in HRNA and HRA participants. Furthermore, there was no significant difference in the plasma beta-endorphin levels between HRNA and HRA participants. Stress, induced a significant increase in plasma beta-endorphin concentration in all four groups of participants. However, the stress-induced increase in plasma beta-endorphin levels was more pronounced in LRNA than HRNA, LRA and HRA participants. Thus, alcohol dependence decreased the basal plasma beta-endorphin levels in LR only, as well as the stress induced increase in plasma beta-endorphin levels of participants without, but not of those with, a family history of alcoholism. Alcohol prior to stress attenuated the stress-induced increase in plasma beta-endorphin levels of all four groups of participants.. The present data indicates that there are differences in both, the basal plasma beta-endorphin levels as well as the response of the pituitary beta-endorphin to stress as a function of family history of alcoholism and alcohol dependence. Thus, in HR individuals a dysfunction in the activity of the pituitary beta-endorphin system predates the development of alcoholism, while in LR individuals it develops following alcohol dependence. Furthermore, alcohol dependence did not alter the alcohol-induced attenuation of beta-endorphin response to stress.

Topics: Adult; Alcohol Drinking; Alcoholism; beta-Endorphin; Child; Child of Impaired Parents; Ethanol; Family; Female; Humans; Male; Pharmacogenetics; Placebos; Psychiatric Status Rating Scales; Risk Factors; Stress, Psychological

1. Plasma oxytocin (OX), vasopressin (VP), estrone (ES) and beta-endorphin (beta-end) levels were measured in 13 male non-chirrotic alcoholics, at 1, 4, 7, 15 and 28 days after alcohol withdrawal and only once in 9 sex- and age-matched normal controls. 2. At all examined time points, plasma OX and ES, but not VP, levels were significantly higher in alcoholics than in controls. Alcoholics showed plasma beta-end levels lower than normal. 3. A positive relationship was found between ES and OX levels suggesting that elevated estrogens levels in chronic alcoholics might exert a stimulatory effect on OX. 4. In light of the well-known effect of OX on learning and memory, an involvement of OX in alcohol-induced neuropsychological deficits may be supposed.

Topics: Adult; Alcoholism; beta-Endorphin; Estrone; Female; Humans; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome; Time Factors; Vasopressins

Previous studies have demonstrated that a moderate dose of ethanol induced a significant increase in the plasma beta-endorphin content of subjects from families with a history of alcoholism (high risk (HR)), but not subjects from families without a history of alcoholism (low risk (LR)). The objective of this study was to examine the response of the pituitary beta-endorphin and adrenal cortisol systems to various concentrations of ethanol in male and female subjects at high and low risk of the future development of alcoholism.. All subjects participated in four experimental sessions. In each session the subjects were given a drink containing one of the following doses of ethanol: 0, 0.25, 0.50, and 0.75 g of ethanol per kilogram of body weight (for a 60- to 70-kg individual). Blood samples were taken at 0 minutes and at 15, 45, 120, and 180 minutes after the drink for estimation of the blood alcohol, plasma beta-endorphin, and plasma cortisol levels.. The concentration of alcohol in the blood at various intervals after the drink was similar among the subjects, regardless of the risk group. Ethanol increased the plasma level of beta-endorphin-related peptides of the HR but not of the LR subjects in a dose-dependent manner. All subjects showed a small decrease in plasma cortisol level with time, but ethanol ingestion did not significantly alter the plasma cortisol levels.. This study indicates that the pituitary beta-endorphin system, but not the adrenal cortisol system, of the HR subjects shows an enhanced sensitivity to ethanol, which may be an important factor in controlling ethanol consumption.

Topics: Adult; Alcohol Drinking; Alcoholism; beta-Endorphin; Biomarkers; Dose-Response Relationship, Drug; Ethanol; Family; Female; Humans; Hydrocortisone; Male; Placebos

We investigated the endogenous opioid system and its role in mediating the reinforcing effects of ethanol that lead to high ethanol consumption as a biochemical marker of an individual's vulnerability to excessive ethanol consumption. We performed studies using human subjects with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism to supplement our studies with experimental animals bred selectively for high- or low-ethanol consumption. HR subjects had lower basal plasma beta-endorphin levels as compared with LR subjects, but they had a more pronounced release of beta-endorphin after exposure to ethanol. Findings from animal studies indicated that ethanol-preferring (C57BL/6) mice (analogous to the HR human subjects) had higher levels of hypothalamic beta-endorphin activity than did ethanol-avoiding (DBA/2) mice (analogous to the LR human subjects) under basal conditions. However, the C57BL/6 mice had a more pronounced release of hypothalamic beta-endorphin than did DBA/2 mice after exposure to ethanol. Thus, although hypothalamic beta-endorphin system activity in human and animal models of alcoholism differs under basal conditions, there is enhanced hypothalamic beta-endorphin system activity after exposure to ethanol in both models. We have also performed studies comparing the density and distribution of opioid receptors in brains of ethanol-preferring animals, such as C57BL/6 mice and ALKO-alcohol (AA) rats, and ethanol-avoiding animals, such as DBA/2 mice and ALKO-non-alcohol (ANA) rats. Interestingly, it was observed that in distinct brain regions known to be important for mediating the process of reinforcement, the C57BL/6 mice had a higher density of delta-opioid receptors than the DBA/2 mice, while the AA rats had a higher density of mu-opioid receptors than the ANA rats. Thus, in the ethanol-preferring animals, the increased release of beta-endorphin following exposure to ethanol was associated with a higher density of delta- or mu-opioid receptors in brain regions important for reinforcement, such as the nucleus accumbens and the ventral tegmental area, and may interact with the dopaminergic system and promote ethanol's reinforcing properties, leading to excessive drinking and alcoholism.

Topics: Alcoholism; Animals; beta-Endorphin; Brain; Brain Mapping; Dopamine; Double-Blind Method; Ethanol; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neural Pathways; Opioid Peptides; Rats; Risk Factors; Selection, Genetic

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

Topics: Adult; Affective Disorders, Psychotic; Alcoholism; beta-Endorphin; Brain; Double-Blind Method; Electric Stimulation Therapy; gamma-Aminobutyric Acid; Humans; Middle Aged; Monoamine Oxidase; Psychoses, Alcoholic

The purpose of the present studies was to investigate the activity of the adrenal gland and the pituitary beta-endorphin system in individuals from families with a 3 generation history of alcoholism, High Risk group, or from families without history of alcoholism, Low Risk group. All subjects had a medical examination, a drinking behavior personal interview and the Michigan Alcoholism Screening Test. Individuals with medical problems or excessive drinking were not included in the study. On the day of testing, a blood sample was taken at 9:00 a.m., then the subject drank a placebo drink or an ethanol solution (0.5 g ethanol/kg B.Wt.). Additional blood samples were taken at 15, 45 and 120 minutes post-drink. Results indicated that individuals of the High Risk group had lower basal levels of beta-endorphin like immunoreactivity (beta-EPLIR) than individuals of the Low Risk group. The dose of 0.5 g ethanol/kg B.Wt. induced an increase in the plasma content of beta-EPLIR of the High Risk group, but not of the Low Risk group. In the Low Risk group ethanol did not induce an increase above the 9:00 a.m. levels, however, it attenuated the beta-endorphin decrease overtime, observed following the placebo drink. Analysis of beta-endorphin-like peptides in the plasma of the High Risk group, with Sephadex G-75 chromatography indicated that the major component of the plasma beta-EPLIR was beta-lipotropin. Plasma cortisol levels, following ethanol intake, presented a small increase in the High Risk group but not in the Low Risk group. Both groups presented similar blood alcohol levels. The basal levels of immunoreactive cortisol and beta-endorphin in the plasma of individuals who were alcoholics, but had been abstinent for at least six months prior to testing were similar to the levels of the High Risk group. Thus there are differences both in the basal levels and in the response of the cortisol and the pituitary beta-endorphin system to an acute ethanol challenge between the two groups.

Topics: Adult; Alcoholism; Analysis of Variance; beta-Endorphin; Chromatography, Gel; Ethanol; Female; Humans; Hydrocortisone; Male; Molecular Weight; Radioimmunoassay; Risk Factors

In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, β-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking.. Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests.. We found significant positive correlations for cotinine and oxytocin (P = .002), β-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking.. These preliminary results suggest a relationship between cotinine and oxytocin, β-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).

Topics: Adult; Alcohol Drinking; Alcoholism; alpha-MSH; beta-Endorphin; Cotinine; Female; gamma-Glutamyltransferase; Humans; Male; Melatonin; Middle Aged; Orexins; Oxytocin; Saliva; Smoking; Substance P; Tobacco Use Disorder

A withdrawal-associated impairment in β-endorphin neurotransmission in the arcuate nucleus (ARC) of the hypothalamus is associated with alcohol dependence characterized by a chronic relapsing disorder. Although acupuncture activates β-endorphin neurons in the ARC projecting to the nucleus accumbens (NAc), a role for ARC β-endorphin neurons in alcohol dependence and acupuncture effects has not been examined. Here, we show that acupuncture at Shenmen (HT7) points attenuates behavioral manifestation of alcohol dependence by activating endorphinergic input to the NAc from the ARC. Acupuncture attenuated ethanol withdrawal tremor, anxiety-like behaviors, and ethanol self-administration in ethanol-dependent rats, which are mimicked by local injection of β-endorphin into the NAc. Acupuncture also reversed the decreased β-endorphin levels in the NAc and a reduction of neuronal activity in the ARC during ethanol withdrawal. These results suggest that acupuncture may provide a novel, potential treatment strategy for alcohol use disorder by direct activation of the brain pathway.

Topics: Acupuncture Therapy; Alcoholism; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Male; Nucleus Accumbens; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Appetite-regulating peptides, such as leptin, are linked to craving and have been in the focus of alcohol dependence research for years. The objective of our study was to investigate the dynamics of leptin gene promoter methylation during alcohol withdrawal and specific treatment in a rodent (rat) model for alcohol dependence. DNA methylation was measured using direct bisulfite sequencing at 0 h, 24 h, and 6 days of alcohol withdrawal as well as after treatment with alpha-melanocyte-stimulating hormone (alpha-MSH), Beta-Endorphin, or saline. We found significantly lower methylation levels in alcohol-consuming animals compared to alcohol-naïve animals. During 6 days of alcohol deprivation, this difference in methylation vanished. Leptin methylation of the alpha-MSH-treated group and 6 days alcohol-deprived animals was significantly higher than that in saline-treated animals, possibly indicating compensatory effects of the treatment. Our results further expand on previous findings from human studies that explain leptin's role in bridging the gap between alcohol consumption and appetite regulation.

Topics: Alcoholism; alpha-MSH; Animals; beta-Endorphin; DNA Methylation; Ethanol; Leptin; Male; Promoter Regions, Genetic; Rats; Substance Withdrawal Syndrome

Alcohol is one of the leading threats to health worldwide. Craving for alcohol makes abstinence a difficult challenge by maintaining alcohol dependence. Many studies suppose the hypothalamic-pituitary-adrenal axis, especially the proopiomelanocortin (POMC)-derived neuropeptides, to mediate craving during withdrawal in alcohol dependence. Evidence is available that the two POMC proteins, α-melanocyte-stimulating hormone (α-MSH) and β-endorphin (β-END) are altered by alcohol consumption and influence alcohol consumption, respectively.. We investigated the dynamics of α-MSH and β-END during alcohol withdrawal and the influence of intraperitoneal administration of either α-MSH or β-END in an established rodent model (Wistar rats) for alcohol dependence.. After long-term alcohol self-administration over 12 months and repeated deprivation periods for 3 days, we found a significant decrease in α-MSH levels during withdrawal in rodents (p = 0.006) compared to controls, while β-END levels remained unchanged. Treatment with intraperitoneally administered α-MSH and β-END did not affect alcohol drinking behavior after deprivation.. We demonstrate the effects of alcohol deprivation on α-MSH in alcohol-dependent rodents, which appear to mimic α-MSH alteration found after fasting periods during appetite regulation. Therefore, low α-MSH levels are a possible indicator for craving in alcohol-dependent individuals and hence would be a potential target for anti-craving treatment.

Topics: Alcohol Drinking; Alcoholism; alpha-MSH; Animals; beta-Endorphin; Disease Models, Animal; Ethanol; Male; Rats, Wistar

Activation of mesolimbic mu-opioid receptors by their endogenous ligand, β-endorphin, can mediate the rewarding effects of alcohol. However, there is conflicting evidence on the relationship between the mu-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) and alcohol dependence risk. Preclinical evidence suggests that sex and sex hormone-dependent prenatal brain organization may interact with the opioid system to influence alcohol drinking behavior. We genotyped 200 alcohol-dependent patients and 240 healthy individuals for the OPRM1 A118G SNP and measured serum β-endorphin level at recruitment and after acute withdrawal. We then determined the association between these factors and alcohol dependence risk and 24-month outcome in the context of both sex and second-to-fourth digit lengths ratio (2D:4D) - a biomarker of prenatal sex hormone levels. The OPRM1 A118G AA genotype associated with elevated risk of alcohol-related hospital readmission, more readmissions, and fewer days until first readmission in male patients only. After normalizing patient 2D:4D against control 2D:4D, we found that normalized 2D:4D ratios were lower in male 118G patients than male AA patients, suggesting prenatal androgens interact with OPRM1 to influence alcohol dependence risk. In addition, β-endorphin levels after acute withdrawal correlated negatively with withdrawal severity in females but not in males, which may indicate β-endorphin protects against withdrawal-induced stress in a sex-specific manner.

Topics: Adult; Alcohol Drinking; Alcoholism; Androgens; beta-Endorphin; Cohort Studies; Female; Fingers; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Organ Size; Patient Admission; Polymorphism, Single Nucleotide; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Opioid, mu; Sex Characteristics; Treatment Outcome

Pharmacological treatment currently used for alcohol dependence is not sufficient for the all patients, and there is a crucial need to find more effective treatments. Recent studies indicate that topiramate is likely the most promising new medication for alcohol dependence. The rationale for topiramate as treatment for alcohol addiction is based on its multifaceted neurochemical activity that targets multiple neural pathways.. This study aims to assess the effect of repeated treatment with topiramate on voluntary alcohol intake and beta-endorphin plasma level in rats selectively bred for high alcohol preference.. Initially, Warsaw high preferring rats (N = 50) were given a 24-h/day free choice between a 10 % (v/v) alcohol solution and water for three consecutive weeks. Subsequently, rats were administered with topiramate (40 or 80 mg/kg b.w.) or vehicle for 14 days and ethanol intake was measured daily. Subsequently, we examined the effects of topiramate on plasma beta-endorphin levels, while alcohol was available and when it was not available for an extended period time.. We observed significantly increase in the levels of beta-endorphin in rats with free access to alcohol both in a topiramate- or vehicle-treated group. However, in topiramate-treated group, a voluntary consumption of alcohol diminished in comparison with the vehicle-treated rats.. The results from this study indicated that topiramate reduces voluntary alcohol intake and support our previous findings that the increase of beta-endorphin level is responsible at least partly for the effectiveness of drugs in treating the alcohol addiction.

Topics: Alcohol Drinking; Alcoholism; Animals; Anticonvulsants; beta-Endorphin; Dose-Response Relationship, Drug; Ethanol; Female; Fructose; Rats; Time Factors; Topiramate

The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

Topics: Alcoholism; beta-Endorphin; Circadian Rhythm; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System

Many recent researches have confirmed the effectiveness of antiepileptic drugs in preventing alcohol dependency, whereas our previous study showed that repeated treatment with topiramate, a new antiepileptic drug, was effective in increasing the plasma levels of beta-endorphin (an endogenous opioid peptide) in rats. It is well documented that in humans a genetic deficit of beta-endorphin is often associated with alcohol addiction as alcohol consumption elevates the level of this peptide. The aim of the present study is multifaceted: to investigate the effect of repeated treatment of levetiracetam (50 or 100mg/kg b.w., twice daily) on voluntary alcohol intake in alcohol preferring rats (Warsaw High Preferring; WHP) and to assess changes in plasma beta-endorphin levels while alcohol is available and when it is not available for an extended period of time. We observed a noticeable increase in the levels of beta-endorphin in rats with free access to alcohol whether in a prolonged levetiracetam-treated or vehicle-treated group. However, in the levetiracetam group, a voluntary intake of alcohol diminished in comparison with both the pretreatment period and in comparison with the vehicle-treated rats. A similar increase in the plasma beta-endorphin levels was observed in levetiracetam-treated rats that did not have access to ethanol. This finding lets us to believe that levetiracetam may be a promising medication in treatment of alcohol dependency as its application leads to the increase in the beta-endorphin concentration and ultimately results in reducing deficiency of this peptide.

Topics: Alcohol Drinking; Alcoholism; Animals; Anticonvulsants; beta-Endorphin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethanol; Female; Humans; Levetiracetam; Piracetam; Rats; Rats, Inbred Strains; Self Administration; Substance Withdrawal Syndrome

Experimental evidence suggests that ethanol alters the activity of the endogenous opioid peptide systems in a dose and brain-region dependent manner. These alterations may influence the processes of ethanol reward and reinforcement. Thus, it was the objective of this study to investigate the response of the 3 major opioid peptide systems (endorphins, enkephalins, and dynorphins) to acute ethanol administration, at the level of the midbrain including the ventral tegmental area (midbrain/VTA), a region important for drug, including ethanol reinforcement.. Using the in vivo microdialysis technique coupled with specific solid-phase radioimmunoassay for beta-endorphin, met-enkephalin, and dynorphin A(1-8,) changes in the extracellular concentration of theses peptides at the level of midbrain/VTA were determined at distinct time points following the administration of 0.0 (saline), 0.8, 1.2, 1.6, 2.0, and 2.4 g ethanol/kg B.Wt.. A biphasic effect of ethanol on beta-endorphin release was found, with low to medium (1.2, 1.6, and 2.0 g) but not high (2.4 g) doses of ethanol, inducing a significant increase in the dialysate content of beta-endorphin. A late increase in the dialysate content of dynorphin A(1-8) was observed in response to the 1.2 g ethanol dose. However, none of the ethanol doses tested significantly altered the content of met-enkephalin in the dialysate.. The present findings suggest that the ethanol-induced increase of beta-endorphin release at the level of midbrain/VTA may influence alcohol reinforcement.

Topics: Alcoholism; Animals; beta-Endorphin; Central Nervous System Depressants; Disease Models, Animal; Dose-Response Relationship, Drug; Dynorphins; Enkephalin, Methionine; Ethanol; Injections, Intraperitoneal; Male; Mesencephalon; Opioid Peptides; Peptide Fragments; Rats; Rats, Sprague-Dawley; Time Factors; Ventral Tegmental Area

Experimental evidence indicates that the endogenous opioid system influences stress responses as well as reinforces effects of addictive drugs. Because stress is an important factor contributing to drug dependence and relapse, we have now studied ethanol preference in enkephalin- and beta-endorphin-deficient mice under baseline conditions and after stress exposure.. In the present study we used a two-bottle choice paradigm to study ethanol consumption and stress-induced ethanol preference. To examine alcohol withdrawal symptoms the forced drinking procedure was employed. We performed an association analysis in two case-control samples of alcohol addicts to determine whether these opioid peptides also contribute to ethanol dependence in humans.. Ethanol consumption was significantly reduced in the absence of beta-endorphins, particularly in female knockout animals. Stress exposure results in an increased ethanol consumption in wild-type mice but did not influence ethanol-drinking in beta-endorphin knockouts. Enkephalin-deficient mice showed no difference from wild-type mice in baseline ethanol preference but also showed no stress-induced elevation of ethanol consumption. Interestingly, we found a two-marker haplotype in the POMC gene that was associated with alcohol dependence in females in both cohorts.. Together these results indicate a contribution of beta-endorphin to ethanol consumption and dependence.

Topics: Adult; Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Body Weight; Choice Behavior; Disease Models, Animal; Enkephalins; Female; Food Preferences; Gene Frequency; Genotype; Humans; Linkage Disequilibrium; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Polymorphism, Single Nucleotide; Pro-Opiomelanocortin; Sex Characteristics; Stress, Psychological

Our previous studies have shown that repeated acamprosate administration to ethanol-naive Warsaw high preferring (WHP) rats resulted in increased plasma beta-endorphin levels and at least partially prevents increases in levels of this peptide after a single administration of ethanol compared with untreated control rats. The objective of the present study, which included 45 WHP rats, was to continue the past research and investigate the effect of 10-day acamprosate treatment (200 mg/kg p.o.) on alcohol intake using a free-choice procedure and on changes in plasma beta-endorphin levels while alcohol is available, and 10 days after alcohol withdrawal. Voluntary alcohol consumption increases plasma levels of beta-endorphin from 440+/-25 pg/ml to 711+/-57 pg/ml (p=0.0002). After a 10-day of alcohol withdrawal, the levels of this peptide were significantly reduced compared with levels in rats with free access to ethanol (711+/-57 pg/ml vs. 294+/-38 pg/ml, p=0.000001) and in control naive rats (440+/-25pg/ml vs. 294+/-38pg/ml, p=0.044). Chronic treatment with acamprosate increased plasma beta-endorphin levels both in WHP rats with free access to ethanol (440+/-25 pg/ml vs. 616+/-49 pg/ml, p=0.008) and in rats after ethanol withdrawal (440+/-25 pg/ml vs. 620+/-56 pg/ml, p=0.007). In the group with free access to ethanol, there was a significant reduction in mean ethanol intake, from 6.75+/-0.20 g/kg body weight/day to 4.68+/-0.25 g/kg/day. Our results indicate that chronic acamprosate treatment may have beneficial effects, as it increases the beta-endorphin concentration thereby compensating for beta-endorphin deficiency during ethanol withdrawal. As the endogenous opioid system has an important role in the development of craving for alcohol, restoring the alcohol-induced deficits in beta-endorphin levels may be an important factor to prevent craving and maintaining abstinence. We suppose that the anti-craving mechanism of acamprosate that has been reported to abolish excessive glutamate release during alcohol withdrawal may be accompanied by compensation for the beta-endorphin deficiency.

Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Animals; Behavior, Animal; beta-Endorphin; Disease Models, Animal; Ethanol; Female; Rats; Taurine; Time Factors

It is well known that alcohol consumption leads to an increase in the levels of beta-endorphin (an endogenous opioid), which can contribute to the reinforcing effect of alcohol. Our previous studies have shown that repeated treatment with naltrexone, a nonselective opioid antagonist, results in increased plasma beta-endorphin levels. Ample studies in animals and humans have shown that naltrexone diminishes ethanol consumption. The aim of the present study in alcohol-preferring rats (Warsaw High Preferring; WHP) was to investigate the effect of 10 days of naltrexone treatment (2 mg/kg i.p.) on voluntary alcohol intake and on changes in plasma beta-endorphin levels while alcohol was available and 10 days after imposed abstinence. It was observed that voluntary alcohol intake induces an increase in plasma beta-endorphin levels in WHP rats. After a 10-day period of alcohol withdrawal, the levels of this peptide were significantly reduced compared with the levels in rats with free access to ethanol and in control alcohol-naïve rats. In chronic naltrexone-treated rats with free access to alcohol, an increase in the levels of this peptide was also observed; however, voluntary alcohol intake was diminished. A similar increase in plasma beta-endorphin levels was observed in naltrexone-treated rats that did not have access to ethanol. As the endogenous opioid system has an important role in the development of a craving for alcohol, it is likely that chronic naltrexone treatment may have a beneficial effect leading to a compensatory increase in the beta-endorphin concentration and ameliorating its deficiency during ethanol withdrawal. Restoring the alcohol-induced deficiency of beta-endorphin may be an important factor in the prevention of craving and maintenance of abstinence. This finding supports the proposition that the endogenous opioid system plays an important role in developing a craving for alcohol.

Topics: Alcohol Drinking; Alcoholism; Analysis of Variance; Animals; Behavior, Animal; beta-Endorphin; Central Nervous System Depressants; Disease Models, Animal; Ethanol; Female; Naltrexone; Narcotic Antagonists; Rats; Time Factors

Clinical and animal studies indicate that selective serotonin-reuptake inhibitors (SSRIs) may help to reduce alcohol intake but investigations led to conflicting results. A few studies indicated that serotonin (5-HT) may modulate the brain beta-endorphin level, which plays an important role in the development of alcohol craving. Our study examined the influence of fluoxetine on the endogenous opioid system. We investigated plasma levels of beta-endorphin in rats with either high alcohol preference (Warsaw High-Preferring; WHP) or low alcohol preference (Warsaw Low-Preferring; WLP) after repeated treatment with fluoxetine (5 mg/kg i.p. for 21 days). We examined the rats 24 hours after fluoxetine treatment in order to determine whether chronic fluoxetine produces a long-term change in the beta-endorphin levels. The animals received either a single dose of ethanol (2 g/kg) or an identical single dose of saline one hour before blood collection. While a few studies observed an increase in the level of beta-endorphin after a single fluoxetine injection, we did not observe any increase in beta-endorphin plasma levels after repeated fluoxetine treatment. We also did not observe any changes in beta-endorphin levels of rats treated with fluoxetine and injected with ethanol. A lack of increase of beta-endorphin levels may explain why fluoxetine has a limited value in the prevention of craving for alcohol.

Topics: Alcoholism; Animals; Antidepressive Agents, Second-Generation; beta-Endorphin; Female; Fluoxetine; Half-Life; Pilot Projects; Rats; Species Specificity

Recent research indicates that topiramate has a role in the treatment of alcohol dependence. Topiramate has multiple mechanisms of action including enhancement of GABA-ergic inhibitory transmission and blocking excitatory glutamate neurotransmission, and modulating voltage-gated sodium and calcium ion channels and inhibiting carbonic anhydrase. In this study, we examined the effect of topiramate on endogenous opioid systems, which have an important role in the development of alcohol dependence. We investigated the beta-endorphin plasma level of animals with high- and low-risks of alcohol dependency after repeated treatment with topiramate. We used the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats, and treated them with topiramate at a dose of 80 mg/kg p.o. for 14 days. In WHP rats treatment with topiramate led to an increase in beta-endorphin plasma levels, which persisted at the same level even after a single injection of alcohol. The level of this peptide with topiramate was lower than in alcohol-injected WHP rats who did not receive topiramate. Beta-endorphin levels in WHP rats after topiramate or topiramate and ethanol treatment were similar to the basal level of this peptide in WLP rats. In WLP rats, topiramate did not prevent the ethanol-induced increase in beta-endorphin plasma level. We propose that administration of topiramate may have different effects on the opioid system involved in dependence according to genetic susceptibilities to alcoholism.

Topics: Alcoholism; Animals; beta-Endorphin; Drug Administration Schedule; Female; Fructose; Neuroprotective Agents; Radioimmunoassay; Rats; Topiramate

Of the factors identified in different studies as the possible causes of alcoholism, heredity appears to be the most important. However, environmental factors can increase or decrease the risk of an individual developing alcohol dependence.. To clarify the possible influence of heredity on alcoholism, we studied the plasma concentration of beta-endorphins in 25 families with alcoholic members: 27 children whose father was alcoholic and 7 whose father and mother were both alcoholics. The results were compared with finding in an age-matched control group of no-drinking adults and normal children in non-drinking families.. The children of alcoholic parents had significantly lower beta-endorphin levels (p < 0.001) than control individuals, and concentrations were especially low when both parents were alcoholics.. We conclude that plasma beta-endorphin concentration may have predictive value in identifying persons likely to become alcoholics.

Topics: Adolescent; Adult; Alcoholism; beta-Endorphin; Biomarkers; Case-Control Studies; Child; Child, Preschool; Family Health; Fathers; Genetic Predisposition to Disease; Humans; Infant; Middle Aged; Mothers

Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific mu-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous beta-endorphin production and induced mu-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of beta-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous beta-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.

Topics: Adult; Alcohol Deterrents; Alcoholism; beta-Endorphin; Cells, Cultured; Disease Susceptibility; Drug Evaluation, Preclinical; Ethanol; Female; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; Hybrid Cells; Leukemia Virus, Murine; Lymphocytes; Male; Middle Aged; Naltrexone; Peptide Fragments; Peptides; Receptors, Opioid, mu; RNA, Messenger; Somatostatin; T-Lymphocytes; Up-Regulation; Virion; Virus Replication

Treatment with acamprosate, a compound used for relapse prevention treatment of alcoholism, was recently shown to be associated with increased plasma concentration of beta-endorphin in rats selectively bred for high alcohol preference. The aim of our study was to prove this result in a comparative clinical study with a corresponding design. We studied 51 alcohol dependent patients following alcohol withdrawal during treatment with acamprosate versus placebo for 4 weeks. Data were analyzed for patients with high alcohol preference (HP) and low alcohol preference (LP) by dichotomizing the sample according to median alcohol intake prior to detoxification. In line with pre-clinical data, beta-endorphin plasma concentration in HP patients was significantly lower compared with LP patients. Four weeks of treatment with acamprosate resulted in a significantly increased beta-endorphin plasma concentration compared with placebo and a significant difference in HP patients but not in LP patients. In conclusion, acamprosate seems to modulate the endogenous opioid system. Our data are in accordance with the assumption that the effect of acamprosate on endorphin plasma concentrations is mainly based on the effect in the high preferring subgroup. Since beta-endorphin deficiency was earlier associated with alcohol craving and anxiety during withdrawal, abstinence maintaining effects of acamprosate might at least be partially related with the ability to modulate opioidergic activity especially in the subsample of HP patients with an attenuated opioidergic activity during this state.

Topics: Acamprosate; Adult; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Biomarkers; Female; Humans; Male; Middle Aged; Placebos; Rats; Taurine

The aim of this study was to evaluate the beta-endorphin (beta-endorphin) plasma level in Warsaw Low Preferring (WLP) and Warsaw high-preferring (WHP) rats after repeated administration of acamprosate, one of most effective drug in the treatment of alcoholism. Treatment with acamprosate in dose 200mg/kg, p.o. for 10 days induced an increase in plasma beta-endorphin levels. A single injection of ethanol also results in the increase of beta-endorphin level. Moreover, it was found that single injection of ethanol to WHP rats resulted in lower increase of plasma beta-endorphin content in rats earlier treated with acamprosate. In WLP rats, repeated acamprosate treatment prevents the ethanol-induced increase in plasma beta-endorphin level. It may be concluded that acamprosate modulates the endogenous opioid system.

Topics: Acamprosate; Alcohol Deterrents; Alcohol-Induced Disorders, Nervous System; Alcoholism; Animals; beta-Endorphin; Brain; Disease Models, Animal; Drug Administration Schedule; Drug Interactions; Ethanol; Female; Genetic Predisposition to Disease; Opioid Peptides; Rats; Taurine; Treatment Outcome; Up-Regulation

Individuals with a family history of alcoholism may present a dysfunction in the activity of the hypothalamic-pituitary-adrenal (HPA) axis that predates the development of alcoholism.. The present study investigated the hypothesis that this HPA-axis dysfunction is associated with alterations in the pattern of the circadian (24 h) secretions of adrenal corticotropic hormone (ACTH), cortisol, and beta-endorphin.. Men with [high risk (HR)] or without [low risk (LR)] family history of alcoholism participated in the study. Blood samples were drawn every 30 min for 24 h for estimation of the plasma hormone levels. Participants ingested meals at predetermined intervals and filled out mood questionnaires prior to the placement of the catheter and 1 h after each meal.. The circadian peaks for beta-endorphin, ACTH, and cortisol occurred between 0800 and 0830 hours in both LR and HR participants. The plasma ACTH and beta-endorphin concentrations were lower in HR than LR participants, while the plasma cortisol concentrations were similar between HR and LR participants. For each hormone, the total 24-h secretion was estimated from the area under the 24-h time-concentration curve (AUC). For ACTH and beta-endorphin, but not the cortisol, AUC were lower in HR than LR participants. LR participants reported being more nervous than HR participants. For the LR participants, but not HR participants, the initial mood ratings of "nervous" were positively correlated with the initial plasma cortisol and beta-endorphin concentrations as well as with the cortisol and beta-endorphin AUC.. HR participants presented lower plasma concentrations as well as lower AUC for beta-endorphin and ACTH but not for cortisol. This suggests a dysfunction of the HPA-axis in HR participants that predates the development of alcoholism and a dissociation between plasma ACTH and cortisol levels as a function of family history of alcoholism.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Alcoholism; beta-Endorphin; Circadian Rhythm; Humans; Hydrocortisone; Male; Reference Values; Risk

This article presents the proceedings of the symposium "Endogenous Opioids and Voluntary Ethanol Consumption: What Have We Learnt From Knock-out Mice?" presented at the meeting of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, in September/October 2004. The organizers and chairpersons were Michael S. Cowen and Carles Sanchis-Segura. The presentations were as follows: (1) Regulation of the Opioid System by Alcohol: Comparison of Alcohol-Preferring and -Nonpreferring Strains by Michael S. Cowen; (2) Endogenous Opioids and Alcohol: Lessons From Microdialysis and Knock-out Mice by M. Foster Olive; (3) From Neurochemistry to Neuroanatomy: The Hypothalamic Arcuate Nucleus as a Main Site for Ethanol-Opioids Interaction by Carles Sanchis-Segura; (4) Sensitivity to Ethanol Is Modulated by beta-Endorphin in Transgenic Mice by Judy E. Grisel, Amanda J. Roberts, and George F. Koob; and () The mu-Opioid Receptor Modulates Acute Ethanol Sensitivity and Ethanol Withdrawal Severity by Sandra Ghozland.

Topics: Alcohol Withdrawal Delirium; Alcoholism; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Brain; Ethanol; Humans; Mice; Mice, Knockout; Mice, Transgenic; Motivation; Receptors, Opioid; Receptors, Opioid, mu

Opioid peptides and glycyl-glutamine (Gly-Gln) have been implicated in the control of ethanol consumption. A recognized beta-endorphin cleavage product, Gly-Gln, inhibits voluntary alcohol consumption when microinjected into the nucleus accumbens (AcbSh) of P rats. To evaluate the site-specific efficacy of Gly-Gln on ethanol consumption following AcbSh application, ethanol preferring (P) rats were allowed to establish individual baseline ethanol/water consumption utilizing a voluntary self-administration paradigm. Subsequent to baseline ethanol consumption being established, bilateral guide cannulae were stereotaxically implanted +1 mm dorsal to the AcbSh for subsequent Gly-Gln (100 nmol/microl) or saline vehicle (1 microl) injections. Alcohol intake, body weight, and water intake were measured at 24 h post-injection intervals. Unilateral Gly-Gln injections reduced ethanol consumption 35.6% (P < 0.05) from pre-established baseline consumption (6.24 +/- 0.64 g/kg to 4.06 +/- 0.28 g/kg). Bilateral Gly-Gln injections further reduced consumption to 51.9% (6.4 +/- 1.0 g/kg to 3.08 +/- 0.65 g/kg at 24 h (P < 0.01) below established baseline values within 24 h without significant changes in body weight or water consumption. Also, the amino acid constituents of the dipeptide had no influence on ethanol consumption behavior; however, Gly-Gln efficacy was shown to be comparable to central beta-endorphin-(1-27) or intraperitoneal (i.p.) naltrexone-induced suppression of ethanol intake. These data indicate that the AcbSh exhibits a site-specific sensitivity to the suppressive actions of Gly-Gln or beta-endorphin-(1-27) injections that modulate voluntary ethanol consumption in P rats. These findings support the broader concept that select forebrain opioid-responsive neural sites may influence the development or expression of alcohol abuse syndromes in animal models or humans.

Topics: Alcohol-Induced Disorders, Nervous System; Alcoholism; Animals; beta-Endorphin; Central Nervous System Depressants; Dipeptides; Disease Models, Animal; Ethanol; Genetic Predisposition to Disease; Narcotic Antagonists; Nucleus Accumbens; Rats; Rats, Mutant Strains; Receptors, Opioid

Auricular acupuncture is a medical method that has been used in the treatment of alcohol addiction. In our study we decided to intensify this method by additional biostimulation of the whole organism. The aim of this study was the therapy of patients with alcohol dependence syndrome. Fifty-three alcoholics were treated with two types of laser stimulation in four sessions. Each session consisted of 20 consecutive daily helium-neon laser neck biostimulations and 10 auricular acupuncture treatments with argon laser (every 2nd day). The Beck Depression Inventory-Fast Screen (BDI-FS) was used to assess their frame of mind before the session and after 2 months of treatment. Moreover, beta-endorphin plasma concentration was estimated five times using the radioimmunoassay (RIA) method. Improvement in BDI-FS and increase in, beta-endorphin level were observed. These results suggest that laser therapy can be useful as an adjunct treatment for alcoholism.

Topics: Acupuncture; Adult; Alcoholism; Analysis of Variance; beta-Endorphin; Female; Humans; Low-Level Light Therapy; Male; Middle Aged; Statistics, Nonparametric; Treatment Outcome

Topics: Alcoholism; Anxiety; beta-Endorphin; Dopamine; Ethanol; Humans; Nerve Net; Neurons; Nucleus Accumbens; Substance Withdrawal Syndrome; Ventral Tegmental Area

Experimental evidence indicates that components of the hypothalamic-pituitary-adrenal (HPA) axis and of the endogenous opioid system, such as beta-endorphin (beta-END), influence alcohol consumption, whereas chronic alcohol abuse alters the activity of both systems. Furthermore, gender and age differences have been reported in the activity of the HPA axis under basal conditions, in response to stress and acute alcohol challenge. The objective of the present studies was to investigate the hypothesis that chronic alcohol consumption alters the activity of the HPA axis and pituitary beta-END as a function of severity of alcohol abuse, gender, and age.. Three age groups of each gender (18-29, 30-44, and 45-60 years old) were recruited. Each age and gender group included four subgroups: (a) nondrinkers, (b) light drinkers, (c) heavy drinkers, and (d) alcoholics in treatment. Demographic characteristics, alcohol consumption, and presence of alcohol dependence were recorded by using a structured interview. Blood samples were taken on the day of the interview. The levels of plasma adrenal corticotropic hormone (ACTH), cortisol, and beta-END were estimated as an index of the activity of the HPA-axis and pituitary beta-END.. Plasma ACTH and beta-END levels were significantly lower in females than males of all age and drinking category groups. Plasma cortisol levels were higher in 18- to 29-year-old female subjects compared with the 18- to 29-year-old male subjects. The plasma ACTH and beta-END levels were lower whereas plasma cortisol levels were higher in heavy drinkers than nondrinkers. This decrease in plasma ACTH and beta-END levels with heavy drinking was more pronounced in female than male subjects of the 30-44 and 45-60 age groups.. Chronic drinking, gender, and age influence the activity of the HPA-axis and pituitary beta-END, which in turn may influence drinking behavior.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Age Factors; Alcohol Drinking; Alcoholism; Analysis of Variance; beta-Endorphin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Sex Factors

Associations between several psychopathological alterations and lowered beta-endorphin(beta E) plasma levels have already been stated in former studies. However, whereas single measures during static conditions generally failed in linking beta E levels with psychopathology, dynamic changes of beta E in particular have been shown to be associated with spells of anxiety and depression. During alcohol withdrawal, a decreased secretion of beta E with a delayed normalization has been reported, but up to now only few data became available regarding the interaction of plasma beta E and psychopathological parameters.. The aim of our study was to test the hypothesis whether beta E during acute alcohol withdrawal is associated with anxiety, depression, and craving.. We observed self-rated anxiety, depression, and craving during alcohol withdrawal and assessed beta E levels (RIA) in a consecutive sample of 60 alcoholics on day 1 and day 14 after onset of withdrawal, and in 30 healthy volunteers. To control for mutual interactions of beta E and the pituitary-adrenocortical hormone secretion, plasma corticotropin (ACTH) and cortisol were also determined.. In accordance with prior studies, beta E was significantly lowered on day 1 and day 14 of alcohol withdrawal relative to controls. Plasma levels of ACTH correlated significantly with beta E in alcoholics at both time points and in controls, without differing significantly between the groups. Self-rated anxiety, depression, and alcohol craving decreased significantly between day 1 and day 14. Levels of beta E were inversely correlated with anxiety day 1 (r=-0.58) and day 14 (r=-0.71). Partial correlation coefficients controlling for ACTH plasma levels revealed that this correlation was largely independent from ACTH. In addition, a significant inverse relationship was found between beta E and craving on day 14 (r=-0.28). No association appeared between beta E and depression.. Our results give first evidence that lowered beta E during alcohol withdrawal may contribute to anxiety as a common disturbance during this state.

Topics: Adrenocorticotropic Hormone; Adult; Alcohol Drinking; Alcoholism; Anxiety; beta-Endorphin; Depression; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Hydrocortisone; Male; Middle Aged; Substance Withdrawal Syndrome; Time Factors

Genetic and environmental factors, such as stress, are important for the initiation and maintenance of heavy drinking, whereas beta-endorphin may be important in controlling alcohol consumption. These studies investigated the response of pituitary beta-endorphin to stress and the effect of alcohol on the stress response in subjects at low (LR) and high (HR) risk of alcoholism, as determined from their family history.. Twenty LR and 20 HR subjects were exposed to stress 30 min after ingestion of either a placebo or an alcohol drink. Plasma beta-endorphin was measured before and for 4 hr after the drink. Changes in the concentration of plasma beta-endorphin after ingestion of the placebo or alcohol drink alone served as controls to compare the stress-induced changes. Pulse and diastolic and systolic blood pressure were also measured.. HR subjects presented higher baseline values of pulse and systolic blood pressure and lower plasma beta-endorphin than LR subjects. Stress induced a small increase in cardiovascular activity, whereas alcohol induced a stronger stimulation. Alcohol before stress did not prevent the stress-induced increase in cardiovascular activity. Stress, but not alcohol, increased the plasma beta-endorphin concentration. LR subjects presented a higher stress-induced increase in plasma beta-endorphin and a faster recovery than HR subjects. Alcohol before stress attenuated the stress-induced increase in plasma beta-endorphin in both LR and HR subjects. This attenuation was stronger in LR subjects.. Thus, there are differences in the response of beta-endorphin to stress and the effect of ethanol on stress responses as a function of a family history of alcoholism.

Topics: Adult; Alcoholism; Analysis of Variance; beta-Endorphin; Blood Pressure; Cardiovascular System; Double-Blind Method; Ethanol; Humans; Male; Pituitary Gland; Risk Factors; Stress, Physiological

Among various approaches to long-term correction of the highest functions of the brain there are two methods that are particularly promising. These included: 1) induction of autoantibodies against the enzymes involved in the metabolism of neuroregulators by means of immunization of respective heterologous enzymes; 2) immunization by covalent conjugates of monomolecular neurotropic compounds and neuropeptides with antigen carriers. The investigations of both methods are reviewed and illustrated in experiments on albino rats during alcoholization and some other processes of pathological behavior formation. Evidence is provided for that behavior can be corrected for several months or longer.

Topics: Alcoholism; Animals; beta-Endorphin; Blood-Brain Barrier; Brain; Female; Growth Hormone; Higher Nervous Activity; Humans; Immunization; Oligopeptides; Rats; Substance-Related Disorders; Time Factors

Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable.. The adrenocorticotropic hormone (ACTH), beta-endorphin (beta-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35 g ethanol/kg body weight (BW) and females consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apart (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones.. Resting plasma levels of all four hormones were within the expected range, and the beta-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was beta-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age.. Taken together with other recent findings, the results suggest that the beta-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism.

Topics: Adult; Alcoholism; beta-Endorphin; Biomarkers; Breath Tests; Central Nervous System Depressants; Ethanol; Female; Genetic Predisposition to Disease; Humans; Male; Twins, Dizygotic; Twins, Monozygotic

Topics: Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Cytotoxicity, Immunologic; Ethanol; Killer Cells, Natural; Lymphoma; Male; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured

Extensive research on both human alcoholics and in animal models of alcoholism has implicated the release of endogenous opioids in the consumption of ethanol. Various experiments using opioid antagonists have indicated that these drugs cause both humans and animals to decrease their consumption of ethanol. However, it remains unclear exactly which of the endogenous opioids mediates the rewarding effects of ethanol. The present experiment used intravenous self-administration of ethanol to determine whether beta-endorphin (BE)-deficient mice differed from wild-type (WT) mice in ethanol self-administration. The BE-deficient mice completely lack BE, but are otherwise similar to the WT mice. By using intravenous self-administration, we were able to rule out any ability of BE to mediate differences in ethanol consumption via palatability factors alone. Both types of mice were 7 generations backcrossed onto a C57BL/6J inbred strain background. During nine daily, 2-hr free-operant sessions, 14 BE-deficient and 17 WT mice could nosepoke for 75 mg/kg ethanol infusions delivered intravenously on an fixed-ratio 3 schedule with a 2-sec time-out after each reinforcer delivery. Reinforcer delivery occurred following nosepokes in only one of two holes. Contrary to what was expected, BE-deficient mice acquired selective operant responding for ethanol, whereas WT mice did not. Although the two genotypes did not differ in either operant or locomotor behavior during the first session, by the end of the nine sessions, BE deficient mice were reliably nosepoking for ethanol, whereas WT mice were not. These findings may indicate that BE is not essential for the postingestive reinforcing effects of ethanol in these animals.

Topics: Alcoholism; Animals; beta-Endorphin; Conditioning, Operant; Ethanol; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Activity; Reinforcement Schedule; Self Administration

Human beta-endorphin-like immunoactivity was measured in highly trained athletes (n = 10), alcoholics in the early phase of abstinence (n=9) and normal controls (n=15) using the Nichols Allegro immunoradiometric assay. The assay was examined for cross reactivity against related peptides, beta-lipotropin and human N-acetyl beta-endorphin. Venous blood sampling was carried out in the morning at 0900 and 1100 hours in a fasting state. Using two-way analysis of variance there was a significant effect of subject group on beta-endorphin concentration (p=0.029). Post-hoc analysis using the Bonferroni t-test showed that the source of the difference was the alcoholic group having significantly lower beta-endorphin immunoreactivity (p < 0.05). There was no difference between the controls and the athletes. There was a positive correlation between plasma beta-endorphin level at 1100 hours and the subsequent ACTH incremental response to naloxone in the group as a whole (r=0.48, p=0.004). The assay showed 100% cross reactivity with beta-lipotropin and 73% cross reactivity with N-acetyl-beta-endorphin. We conclude that alcoholics have reduced levels of beta-endorphin-like immunoactivity. While beta-endorphin is known not to cross the blood-brain barrier, levels of plasma beta-endorphin-like immunoactivity may indirectly reflect central opioid activity.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; beta-Endorphin; beta-Lipotropin; Body Mass Index; Fasting; Female; Humans; Immunoradiometric Assay; Male; Naloxone; Narcotic Antagonists; Sensitivity and Specificity; Sports

Chronic alcohol drinking causes profound alterations in hypothalamic-pituitary function. In the present study, endocrine [corticotropin (ACTH), beta-endorphin, cortisol, and met-enkephalin] and cardiovascular (blood pressure) changes in response to hyperthermic stress (sauna at 90 degrees C for 30 min) were evaluated in 25 normal men (25 to 50 years old) and in 48 male alcoholic subjects (34 to 56 years old) after 5 weeks of abstinence. Significantly lower increments in systolic blood pressure were observed in alcoholics than in control subjects. Furthermore, alcoholics showed lower ACTH, beta-endorphin, and cortisol increments in response to sauna than normal controls. In contrast, sauna-induced hyperthermia did not change significantly the circulating met-enkephalin levels in either normal controls or chronic alcoholics. These data suggest that an impairment in the adaptive response to stress affects alcoholic men even after a few weeks of abstinence from alcohol.

Topics: Adaptation, Physiological; Adrenocorticotropic Hormone; Adult; Alcoholism; Arousal; beta-Endorphin; Enkephalin, Methionine; Ethanol; Heat Exhaustion; Humans; Hydrocortisone; Hyperthermia, Induced; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System

The circadian secretion of beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol was evaluated in 14 non-cirrhotic alcoholic men after 7 and 28 days of abstinence and in 12 sex- and age-matched normal subjects. A significant decrease in plasma levels of beta-endorphin, reduced ACTH levels, and increased cortisol levels were observed in samples taken at 08.00 h, 12.00 h, 18.00 h, and 23.00 h both after 7 and 28 days of abstinence. These data suggest the presence of a strong negative feedback on pro-opiomelanocortin synthesis by cortisol hypersecretion in abstinent alcoholics, which might be due to long-term stimulation of adrenal function by alcohol. The decreased plasma beta-endorphin levels might predispose to relapse in alcohol abuse.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; beta-Endorphin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Pro-Opiomelanocortin; Recurrence; Risk Factors

Several reports have speculated that variations in beta-endorphin functioning may actually proceed the development of alcoholism and other drug use disorders, and is consequently a genetic mechanism of some etiologic importance. The goal of this investigation was to determine whether differences in basal plasma beta-endorphin concentrations could be confirmed in prepubertal children naive to alcohol and drugs, yet at parental risk for alcoholism, or drug dependence. Consequently, we have examined fasting basal plasma beta-endorphin concentrations in a sample of prepubertal sons of alcoholic fathers and compared them to both our existing sample of sons of drug dependent fathers and normal control boys. In addition, we examined the relationship between plasma beta-endorphin concentrations and maternal reports of problem behaviors posited to be related to the liability for alcoholism or drug abuse. The results reveal no differences in fasting basal plasma beta-endorphin concentrations. Although the at-risk groups differ significantly from normal boys having elevated scale scores for internalizing and externalizing problem behaviors, no association between plasma beta-endorphin and these behavioral risk factors could be found. Overall, the results fail to support an inherited 'opioid deficiency hypothesis' for the development of alcoholism or drug dependence.

Topics: Alcoholism; Analysis of Variance; beta-Endorphin; Biomarkers; Case-Control Studies; Child; Child Behavior Disorders; Child of Impaired Parents; Family Health; Fathers; Humans; Male; Prospective Studies; Risk Factors; Substance-Related Disorders

It is well-established that the secretion of the opioid neuropeptide beta-endorphin is perturbed by the administration of various drugs of abuse. Several investigators have speculated that variations in beta-endorphin secretory regulation may precede the development of a substance use disorder, and thus be a component of the liability for substance abuse. In order to test this hypothesis, we examined fasting, morning plasma concentrations of beta-endorphin and two catecholamine metabolites in prepubertal boys naive to drugs of abuse and at elevated familial risk for a substance use disorder (SA+), and in controls (SA-). Specifically, the dopaminergic metabolite homovanillic acid (pHVA), and the noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (pMHPG) were measured. Between-group differences were not found for beta-endorphin, pHVA, or pMHPG. Similarly, such differences did not differentiate sons of fathers with Antisocial Personality Disorder and controls. However, regression analysis revealed that although both pHVA and pMHPG predicted beta-endorphin concentrations to similar degrees, the directions of influence were the opposite. pHVA was found to be positively associated with beta-endorphin while pMHPG was found to be negatively associated with beta-endorphin. No between-group differences in these relationships were found. The results suggest an opponent process in catecholaminergic regulation of beta-endorphin in humans, and are consistent with observations in the central nervous system of animal models.

Topics: Alcoholism; Antisocial Personality Disorder; beta-Endorphin; Child; Child of Impaired Parents; Fathers; Homovanillic Acid; Humans; Illicit Drugs; Male; Methoxyhydroxyphenylglycol; Personality Assessment; Psychotropic Drugs; Risk Factors; Substance-Related Disorders

Topics: Adrenocorticotropic Hormone; Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Fetal Alcohol Spectrum Disorders; Gene Expression; Humans; Hypothalamo-Hypophyseal System; Immunocompetence; Pregnancy; Pro-Opiomelanocortin; Signal Transduction

Susceptibility to alcoholism varies with age, gender, and familial background. Youthful nonalcoholic males with multigenerational family histories of male alcoholism seem at particular risk. Previous investigations suggest that such males are characterized by abnormal psychophysiological response, while sober and alcohol-intoxicated; additional recent studies indicate that the endogenous opiate systems are involved in mediating ethanol reinforcement and modulating intake. We first compared cardiac response to alcohol administration among young (mean = 22.8 years), nonalcoholic men and women with multigenerational, unigenerational, and negative family histories of alcohol dependence and abuse. Then, we compared the ethanol-induced cardiac response of the males in these three groups to that of currently alcohol-dependent older males and age-matched nonalcoholic male controls. Finally, we examined ethanol-induced change in plasma beta-endorphin and cortisol levels among a subset of the nonalcoholic males, divided into those with high and low levels of postethanol administration heart-rate increase. Nonalcoholic males with multigenerational family histories of male alcoholism were characterized by significantly higher [t(301) = 5.70, p < 0.0001, Cohen's d = 0.73] levels of ethanol-induced heart-rate increase than nonalcoholics from all other comparison groups. The magnitude of their increase matched that of current male alcohol-dependents. Nonalcoholic males with high levels of ethanol-induced heart-rate increase also produced significantly more plasma beta-endorphin after consuming alcohol. Peak production of beta-endorphin was highly correlated (r = 0.861, p < 0.001) with magnitude of heart-rate increase. A subset of those at risk for alcoholism may be characterized by sensitivity to ethanol-induced reward, marked by heightened ethanol-induced, heart-rate increase, mediated by ethanol stimulation of endogenous opiate production. This subset might contain those who, once alcoholic, would differentially benefit from treatment with opiate antagonists.

Topics: Adult; Alcohol Drinking; Alcoholism; beta-Endorphin; Child of Impaired Parents; Disease Susceptibility; Dose-Response Relationship, Drug; Endorphins; Ethanol; Family; Female; Genetic Predisposition to Disease; Heart Rate; Humans; Hydrocortisone; Male; Narcotic Antagonists; Sex Factors; Stimulation, Chemical

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4+ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and beta-endorphin pretreatment on the activation of CD4+ lymphocytes endowed with the homing receptor CD62L.

Topics: Alcoholic Intoxication; Alcoholism; beta-Endorphin; CD4 Antigens; CD4-Positive T-Lymphocytes; Cell Adhesion; Cell Line; Cell Movement; Dipeptidyl Peptidase 4; Ethanol; Humans; Immunocompetence; In Vitro Techniques; Interleukin-2; Lymphocyte Activation; Receptors, Immunologic; Recombinant Proteins; T-Lymphocytes; Tumor Cells, Cultured

Studies investigating the influence of chronic ethanol treatment on the beta-endorphin content and the proopiomelanocortin (POMC) gene expression in the rat pituitary revealed contradictory results. Because of this we decided to start a more complex study to investigate the effects of isolation stress, chronic ethanol treatment and voluntary ethanol consumption on the POMC mRNA level in the rat pituitary. The immediately prepared total RNA from rat pituitaries was used in hybridization experiments (Northern- and Dot-blots). The results suggest a correlation between the POMC gene expression and the different fashions of 'living conditions' tested. So the POMC gene expression in long-term alcohol-treated animals was decreased supporting the theory of beta-endorphin deficiency in alcoholism. More interestingly, data obtained from the group of voluntary ethanol consumption suggest an inverse correlation between total ethanol ingestion and POMC gene expression. This indicates the importance of the method of ethanol administration. Consistent with a decreased POMC gene expression in the pituitary during chronic ethanol treatment are previous studies showing a decrease in the plasma beta-endorphin content in such situations. Surprisingly, in the present study the plasma beta-endorphin levels measured by radioimmunoassay were only slightly decreased in chronically ethanol-treated rats. This may be due to dysregulatory effects of ethanol on post-translational processing, degradation and/or release of beta-endorphin.

Topics: Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Gene Expression; Male; Pituitary Gland; Pro-Opiomelanocortin; Protein Processing, Post-Translational; Rats; Rats, Wistar; RNA, Messenger

Previous studies demonstrated that both the spontaneous and ethanol-stimulated release of beta-endorphin (beta-EP) like-peptides (beta-EPLPs) by the hypothalami of the ethanol-preferring C57BL/6 mice is more pronounced than by the hypothalami of the ethanol-avoiding DBA/2 mice. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the in vitro release of beta-EP peptides by the hypothalami of the ethanol-preferring Alko-Alcohol (AA) and ethanol-avoiding Alko Non-Alcohol (ANA) lines of rats. Results indicated that although the spontaneous release of hypothalamic beta-EPLPs was higher by the ANA than by the AA rats, the percentage increase following exposure to various concentrations of ethanol was similar in both lines of rats. Furthermore, the release of hypothalamic beta-EPLPs following exposure to 30 mM ethanol was significantly higher than the release following exposure to 10 mM ethanol in the AA, but not the ANA, rats. Analysis of the released beta-EPLPs with Sephadex G-75 and reversed phase HPLC indicated that the nonacetylated beta-EP 1-31 was the major component in the hypothalamic perifusates of the AA rats, whereas the shorter and acetylated forms of beta-EP were the predominant components in the hypothalamic perifusates of the ANA rats. Because the shorter and acetylated forms of beta-EP are devoid of opioid activity, their pronounced release by the hypothalami of the ANA rats may be important in maintaining their low ethanol consumption, even after long-term access to ethanol solutions.

Topics: Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Culture Techniques; Dose-Response Relationship, Drug; Female; Hypothalamus; Male; Motivation; Peptide Fragments; Phenotype; Rats; Rats, Inbred Strains; Receptors, Opioid; Selection, Genetic

Endogenous opioid peptides are known to be involved in the alcohol tolerance and dependence following alcohol abuse. However, the cellular mechanisms involved in the ethanol tolerance and dependence are not well established. We have previously shown that low concentrations of ethanol stimulate immunoreactive beta-endorphin (IR-beta-EP) release from the cultured hypothalamic neurons and that chronic ethanol exposure desensitizes these neurons to ethanol challenges. In this study, we determined the IR-beta-EP response to increasing doses of ethanol during the desensitizing phase of moderate ethanol doses to test whether the cultured IR-beta-EP-secreting neurons develop tolerance to ethanol following constant exposure. We also determined IR-beta-EP responses following withdrawal from chronic ethanol challenge and compared the IR-beta-EP secretory response to various doses of ethanol in ethanol-naive and ethanol-preexposed cultures. The IR-beta-EP responses to increasing doses of ethanol (50-150 mM) were markedly reduced in the cultures preexposed to a 50 mM dose of ethanol when compared with those that were naive to ethanol. The ethanol-exposed cultures showed hypersecretion of IR-beta-EP after removal from 48 hr of constant ethanol, as compared with ethanol-naive cultures. When ethanol-preexposed cultures were challenged with various doses of ethanol 4 days after ethanol withdrawal, the cultures showed higher IR-beta-EP secretory responses than did the ethanol-naive cultures. These data suggest that IR-beta-EP secretory neurons in primary cultures develop tolerance to chronic ethanol, show withdrawal response after removal of chronic ethanol exposure, and develop sensitization following repeated ethanol challenges.

Topics: Alcohol Withdrawal Delirium; Alcoholism; Animals; beta-Endorphin; Cell Survival; Culture Techniques; Dose-Response Relationship, Drug; Drug Tolerance; Ethanol; Female; Fetus; Hypothalamus; Neurons; Pregnancy; Radioimmunoassay; Rats; Rats, Sprague-Dawley

This paper discusses the role of endogenous opioids in response to hyperthermia and the alterations observed in drug or alcohol addicts. Endorphins, rather than enkephalins are involved in adaptation to heat in the central nervous system. The pituitary secretion of beta endorphin together with ACTH in response to thermal stress provided the opportunity to measure the opioid reactivity to hyperthermia in health and toxicomania, as an index of opioid function, in adaptation to heat. The review of the data in the literature shows absent responses of beta endorphin and its related hormone ACTH to the thermal stress of sauna in heroin, cocaine or alcohol addicts. A common explanation for this phenomenon is that the long-term stimulation of hypothalamic opioid neurotransmission that is produced directly or indirectly by heroin, alcohol or cocaine, disrupts the opioid response to thermal stress, and thus the adaptation to heat.

Topics: Adrenocorticotropic Hormone; Alcoholism; beta-Endorphin; Cocaine; Fever; Healthy Worker Effect; Heroin Dependence; Hot Temperature; Humans; Male; Stress, Physiological; Substance-Related Disorders

Plasma beta-endorphin, met-enkephalin and ACTH concentrations were measured in 20 male alcoholics (age: 32-60 yr; duration of ethanol addiction: 13.2 +/- 6.2 yr; mean +/- SE) immediately after admission to the hospital (at a time not exceeding 8 hr from the last ethanol consumption) and after 5 weeks of forced abstinence. The results were compared with those obtained in 12 age-matched normal controls. Plasma ACTH and met-enkephalin levels were normal in alcoholics on both occasions. In contrast, in samples taken at admission to the hospital, the circulating concentrations of beta-endorphin in alcoholics were half (17.1 +/- 5.3 pg/ml; mean +/- SE) of those observed in the normal controls (34.1 +/- 6.0). beta-endorphin levels rose significantly after 5 weeks of abstinence (30.1 +/- 4.9); at this time, they were not significantly different from those observed in normal controls. These data indicate that acute alcohol consumption induces significant alterations in plasma beta-endorphin, but not met-enkephalin levels, which are reversed after 5 weeks of abstinence.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholic Intoxication; Alcoholism; beta-Endorphin; Enkephalin, Methionine; Humans; Male; Middle Aged; Substance Abuse Treatment Centers

beta-endorphin, adrenocorticotrophin, and alpha-melanocyte stimulating hormone were measured by radioimmunoassay in three areas of human brain at necropsy in seven subjects with Wernicke-Korsakoff syndrome and in 52 controls. Thiamin concentration in six brain areas was also measured. Mamillary body beta-endorphin concentrations were significantly increased in those with the syndrome compared with controls, and those controls with high alcohol intake showed increased mamillary body beta-endorphin compared with controls with low alcohol intake. Brain thiamin concentration was similar in both groups, with the exception of the brainstem, where it was reduced in subjects with Wernicke-Korsakoff syndrome. Thalamic beta-endorphin in controls was inversely correlated with thiamin in frontal white matter, frontal cortex, parietal white matter and parietal cortex, while beta-endorphin in the hypothalamus of patients was inversely correlated with thiamin in frontal cortex, parietal white matter, thalamus and brainstem. These results suggest that there is a disturbance of the endorphinergic system in Wernicke-Korsakoff syndrome which may be related to alcohol intake.

Topics: Adrenocorticotropic Hormone; Aged; Alcohol Amnestic Disorder; Alcoholism; alpha-MSH; Autopsy; beta-Endorphin; Brain; Female; Humans; Male; Middle Aged; Radioimmunoassay; Thiamine; Wernicke Encephalopathy

The plasmatic concentration of beta-endorphins and ACTH were measured in 31 alcoholic patients and in a control group (N = 16), to test the possible relation between chronic alcohol intake and propiomelanocortin production. There were found a decrease of beta-endorphins plasmatic levels in chronic alcoholic group, apart of clinical manifestations or abstinence period (one month maximum). This decrease can be cause by the chronic alcohol intake, and can be mediated by the tetrahydroisoquinolines (TIQs) or otherwise be the cause and not the consequence of alcoholism. The global plasmatic levels of ACTH were decreased but it was significant in the subgroup of alcoholics with liver disfunction, mental illness and those who carry on drinking.

Topics: Adrenocorticotropic Hormone; Alcoholism; beta-Endorphin; Humans; Pro-Opiomelanocortin

In order to investigate the neurochemistry of panic disorder in alcoholics, we measured various cerebrospinal fluid (CSF) parameters in subjects with both conditions and compared them with an age- and sex-matched population of alcoholics and normal controls. When height, age and weight were covaried, subjects with panic disorder had higher levels of B-endorphin in CSF. There were no differences in other CSF measures between the groups. Alcoholics with panic disorder had higher plasma MHPG concentrations compared with alcoholics without panic disorder but these were not statistically different from controls.

Topics: Adult; Alcoholism; Anxiety Disorders; beta-Endorphin; Diazepam Binding Inhibitor; Fear; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Longitudinal Studies; Male; Methoxyhydroxyphenylglycol; Neuropeptides; Neurotransmitter Agents; Norepinephrine; Panic

The course of plasma cortisol and beta-endorphin-like immunoreactivity (beta-EP-IR) was determined following a single i.v. administration of 20 mg naloxone. The test subjects included 20 male alcoholics (medication-free), investigated one to three days and four weeks after the onset of abstinence, as well as 10 short-time abstinent alcohol abusers and 10 healthy control subjects. The mean baseline values of cortisol and beta-EP-IR remained within normal limits in all groups. The significant decrease in the plasma cortisol baseline values in the alcoholics after 4 weeks abstinence may indicate a lower level of the regulation of the hypothalamic-pituitary-adrenal axis (HPA) under conditions of abstinence. After naloxone administration an increase in plasma cortisol and beta-EP-IR was observed in all groups. The multivariate trend analysis showed significant differences in the time course of plasma cortisol between the three groups, however not in the course of beta-EP-IR. The changes in the dynamic regulation of the HPA axis, resulting from chronic alcohol consumption, appears to be irrespective of whether the drinking pattern is dependent or abusive. In alcoholics these changes could still be identified following a 4-week abstinence period.

Topics: Adaptation, Physiological; Adult; Alcoholism; Analysis of Variance; beta-Endorphin; Diagnosis, Differential; Discriminant Analysis; Drug Evaluation; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Male; Middle Aged; Naloxone; Pituitary-Adrenal System; Temperance

An alpha-theta brainwave biofeedfack training program was applied as a novel treatment technique for chronic alcoholics. Following a temperature biofeedback pretraining phase, experimental subjects completed 15 30-min sessions of alpha-theta biofeedback training. Compared to a nonalcoholic control group and a traditionally treated alcoholic control group, alcoholics receiving brainwave training (BWT) showed significant increases in percentages of EEG record in alpha and theta rhythms, and increased alpha rhythm amplitudes. Alcoholics receiving BWT showed a gradual increase in alpha and theta brain rhythms across the 15 experimental sessions. These experimentally treated alcoholics showed sharp reductions in self-assessed depression (Beck's Depression Inventory) compared to the control groups. Alcoholics receiving standard medical treatment (abstinence, group psychotherapy, antidepressants) showed a significant elevation in serum beta-endorphin levels at the conclusion of the experiment. This neuropeptide is an index of stress and a stimulant of caloric (e.g., ethanol) intake. Application of brainwave treatment, a relaxation therapy, appears to counteract the increase in circulating beta-endorphin levels seen in the control group of alcoholics. 13-month follow-up data indicate sustained prevention of relapse in alcoholics that completed alpha-theta brainwave training.

Topics: Alcoholism; Alpha Rhythm; beta-Endorphin; Biofeedback, Psychology; Depressive Disorder; Electroencephalography; Follow-Up Studies; Humans; Psychiatric Status Rating Scales; Socioeconomic Factors

Action of ethanol on animals with different predisposition to alcohol consumption depended on the level of ethanol metabolism or sensitivity of nervous system to alcohol. There was studied the ethanol effects on contraction of rat vas deferens. Such an approach enables to distinguish the metabolic effects from action on nervous system. It was shown, that dose of ethanol, which inhibits the contraction of rat vas deferens of by 50% is the same in both groups of rats, but the ED50 of adenosin and beta-endorphin were 1.7 and 4.7 times lower for vas deferens of predisposed rats. It's possible to suggest the differences between two groups of rats to be connected with the effects of ethanol on purinergic and endorphinergic system, but not with ethanol itself.

Topics: Adenosine; Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Depression, Chemical; Disease Susceptibility; Ethanol; Male; Muscle Contraction; Rats; Time Factors; Vas Deferens

Beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) plasma concentrations were examined in ten chronic alcohol abusers, eight men and two women aged 25-56 years with histories of continuously elevated ethanol consumption dating from 5-30 years. Plasma levels of the two peptides were measured after acute alcohol consumption and then after 3, 6 and 9 days of forced abstinence, during chlordiazepoxide treatment. Beta-EP and beta-LPH concentrations were normal on all four occasions. A reduced sensitivity of opioid receptors to acute alcohol administration due to chronic alcohol consumption is suggested.

Topics: Adult; Alcohol Withdrawal Delirium; Alcoholic Intoxication; Alcoholism; beta-Endorphin; beta-Lipotropin; Female; Humans; Male; Middle Aged; Naloxone; Psychoses, Alcoholic; Receptors, Opioid

beta-Endorphin was measured in the plasma of control subjects and 12 chronic alcoholics in the acute stage of ethanol intoxication. Naloxone was administered and the level of beta-endorphin was compared before and after treatment. The increased level of beta-endorphin in the intoxicated subjects supports the presence of ethanol interactions with the opioid system, since pituitary secretion does not seem to be involved. Furthermore, the coexistence of high levels of beta-endorphin and an effective naloxone response suggest a possible link between the two.

Topics: Adult; Alcoholism; beta-Endorphin; Endorphins; Ethanol; Humans; Naloxone; Radioimmunoassay

Evidence is accumulating that hormonal systems present in the pituitary and the brain play a critical role in behavioral homeostase. The hormones and their fragments, called neuropeptides, produced by these systems modulate neurotransmitter activity and thereby control brain functions. Disturbances in this hormonal control may result in psychopathology, including addiction. Vasopressin and related peptides decrease under certain conditions addictive behavior of experimental animals and humans and brain reward. The pituitary and brain opioid peptides are candidates to play an essential role in reward processes and may be common factors in addiction to various psychoactive drugs, including heroin and alcohol, and to habits. Other pituitary hormones, like ACTH, gamma 2-MSH and prolactin have also been implicated in brain reward and drug addiction. It is postulated that disturbances in the hormonal and neuropeptide systems may lead to a state in which addiction behavior can easily be elicited and that the hormonal climate in the body may be of relevance for the individual susceptibility to addictive drugs. It is proposed to analyse the relation between hormonal systems and addictive behavior.

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Arginine Vasopressin; beta-Endorphin; Brain; Endorphins; Haplorhini; Heroin Dependence; Humans; Melanocyte-Stimulating Hormones; Naltrexone; Neurotransmitter Agents; Peptides; Pituitary Gland; Rats; Reinforcement, Psychology; Reward; Substance-Related Disorders

beta-Endorphin-like immunoreactivity (BE-LI) was measured in 7 brain regions of Swiss-Webster mice after 24, 48 and 72 h of exposure to ethanol vapor following a priming injection of ethanol and daily injections of pyrazole HCl to inhibit ethanol metabolism. Control mice in identical chambers received pyrazole injections but breathed air only. Ethanol dependence was confirmed by scoring additional groups of mice for handling-induced convulsions during withdrawal after each exposure duration. Measurement of anterior and neurointermediate (NIL) pituitary BE-LI, alpha-MSH and ACTH and plasma corticosterone confirmed earlier results showing NIL depletion of all 3 peptides at 24 h and increased plasma corticosterone concentrations at 72 h in ethanol-exposed mice. In brain extracts from ethanol-dependent mice, BE-LI was significantly reduced in the hypothalamus and midbrain with the greatest reduction occurring at 24 h. In forebrain, cerebral cortex, septum and hippocampus, pyrazole treatment significantly reduced BE-LI relative to an unhandled control group, and ethanol exposure tended to reverse this effect. HPLC of hypothalamic extracts revealed no differences in proportions of molecular forms of beta-endorphin-like peptides between 24 h control and ethanol-exposed groups. The predominant BE-LI peak in both groups co-eluted with opiate-active unmodified beta-endorphin. Ethanol dependence in mice is associated with regionally selective decreases in brain beta-endorphin concentration.

Topics: Alcoholism; Animals; beta-Endorphin; Biotransformation; Brain Chemistry; Chromatography, High Pressure Liquid; Corticosterone; Endorphins; Male; Mice; Peptide Fragments; Pituitary Gland; Pro-Opiomelanocortin

Radioimmunoassay was used to measure the blood content of beta-endorphines in patients with chronic alcoholism. The concentration of endogenous ethanol in these patients was determined by gas chromatography. The blood concentration of beta-endorphines was found to be high in patients who showed atypical affective disorders off the period of abstinence. It is assumed that peripheral beta-endorphine is not linked with the development of the narcomanic syndrome proper but mirrors the pathogenetic mechanisms of psychopathological disorders. The levels of endogenous ethanol vary in alcoholics and healthy subjects within the same ranges. However, the percentage distribution indicates that in patients, they are shifted toward lower concentrations, which is likely to be conditioned by the induction of enzymatic systems that metabolize ethanol.

Topics: Adult; Alcoholism; beta-Endorphin; Chromatography, Gas; Endorphins; Ethanol; Humans; Male; Psychopathology; Radioimmunoassay; Time Factors

Acute ethanol treatment induced a significant increase in the tissue levels of immunoreactive (ir-) Met-enkephalin in hypothalamus, striatum and midbrain, but not in hippocampus. Levels of ir-dynorphin, ir-alpha-neo-endorphin and ir-beta-endorphin were not found to be significantly altered in brain and pituitary. Chronic ethanol treatment (by the use of ethanol liquid diet) resulted in a more than 50% decrease of the tissue levels of ir-dynorphin and ir-alpha-neo-endorphin in hypothalamus and hippocampus, while both peptides remained unchanged in midbrain, striatum, adenohypophysis and neurointermediate pituitary. In contrast, ir-met-enkephalin was decreased in striatum and hypothalamus, but unaffected in midbrain and hippocampus. Levels or ir-beta-endorphin remained unchanged in the brain and in the pituitary. However, the de novo biosynthesis of beta-endorphin and its prohormones beta-lipotropin and pro-opiomelanocortin was increased in the intermediate pituitary and to an even more pronounced degree, in the adenohypophysis, after chronic treatment of rats with ethanol liquid diet, nevertheless, the amounts of opiate-active beta-endorphin were found to be reduced in both lobes of the pituitary: In the adenohypophysis, this was due to a retardation of the enzymatic processing of beta-endorphin from its precursor beta-lipotropin, while in the intermediate pituitary the alpha-N-acetylation of beta-endorphin to opiate-inactive alpha-N-acetyl-beta-endorphin was stimulated. In conclusion, acute and chronic ethanol treatment caused selective alterations on different opioid peptide systems within distinct areas of the rat brain and pituitary.

Topics: Acetylation; Alcoholism; Animals; beta-Endorphin; Brain; Dynorphins; Endorphins; Enkephalin, Methionine; Ethanol; Humans; Male; Peptides; Pituitary Gland; Protein Precursors; Rats; Rats, Inbred Strains; Receptors, Opioid

The concentration of beta-endorphin was determined in the cortex of the large hemispheres, thalamus, striatum and medulla oblongata of rats with varying duration of ethanol anesthesia and after a single injection of ethanol (2.5 g/kg). The content of beta-endorphin was also measured in the brain of rats which preferred and rejected 15% ethanol during long-term (up to 10 months) alcoholization. The data obtained indicate that ethanol produces a specific effect on the endorphinergic system in different brain structures of animals predisposed to voluntary alcoholization. A possible involvement of the neuropeptide in the formation of alcohol tolerance and physical dependence is discussed.

Topics: Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Brain; Endorphins; Ethanol; Humans; Injections, Intraperitoneal; Male; Motivation; Rats; Time Factors

In 34 chronic alcoholics, subdivided into two groups according to the state of the blood-brain barrier (BBB), beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), ACTH and cortisol levels were determined in basal conditions in the plasma and cerebrospinal fluid (CSF). Hormonal concentrations were correlated with brain damage and mnesic function. The results indicate the reduced CSF beta-EP content in chronic alcoholics and suggest that peripheral beta-EP may penetrate into the CSF compartment when there is BBB damage. They also sustain the different origins of central and peripheral pro-opiocortin-related peptides, and support the concept that beta-EP, beta-LPH and ACTH may be autonomously regulated at the central level. Moreover, both morphological brain damage and mnesic impairment in chronic alcoholics are unrelated to CSF peptide levels. The role of opioid peptides in the nature of alcohol-seeking behavior is supported.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Alcoholism; Atrophy; beta-Endorphin; beta-Lipotropin; Brain; Brain Damage, Chronic; Endorphins; Humans; Male; Middle Aged; Tomography, X-Ray Computed

beta-Endorphin-like immunoreactivity in cerebrospinal fluid(CSF) was observed to decrease in patients with Huntington's disease and dementia due to brain vascular disease. The greatest decrease was seen in patients with presenile and senile dementia of Alzheimer type(SDAT). The immunoreactivity significantly correlated with psychological functions when examined using a dementia rating scale (r=0.51, p less than 0.01, for all dementia, r=0.65, p less than 0.02, for only SDAT). These results suggest that a B-endorphin-like substance may be related in the pathophysiology of dementia.

Topics: Adult; Aged; Alcoholism; Alzheimer Disease; beta-Endorphin; Cerebrovascular Disorders; Dementia; Endorphins; Female; Humans; Huntington Disease; Male; Middle Aged

Resting pituitary levels of beta-endorphin-(beta-EP-IR), ACTH-(ACTH-IR), and alpha-MSH-(alpha-MSH-IR)-like immunoreactive material were found to differ among 16 inbred mouse strains. Hormone levels correlated genetically with severity of withdrawal from ethanol, which also differed among the strains. Ethanol dependence led to reduced pituitary beta-EP-IR in 4 of 5 strains studied. After 24 hr of withdrawal, 3 of those 4 showed elevated pituitary beta-EP-IR. These results are consistent with the hypothesis that genetically-determined difference in pituitary hormone functioning underlie some of the genetically-determined differences in ethanol withdrawal severity.

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; beta-Endorphin; Endorphins; Ethanol; Humans; Male; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred Strains; Pituitary Gland; Seizures; Substance Withdrawal Syndrome

The effects of ethanol dependence and withdrawal on pituitary hormone content and corticosterone release were investigated in AKR/J male mice in a vapor chamber. Both chronic ethanol inhalation and ethanol withdrawal were associated with increased adenohypophyseal-adrenocortical activity. Operationally, ethanol exposure was a stressor. Both physical dependence and withdrawal led to increased secretion/synthesis ratios of peptide hormones. The temporal pattern of pituitary ACTH-IR content changes was different from that of beta-endorphin-IR and alpha-MSH-IR. Differences in the pattern of ACTH-IR and alpha-MSH-IR most probably represent lobe-specific differences in the response to chronic ethanol exposure and withdrawal.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Alcoholism; Animals; beta-Endorphin; Corticosterone; Endorphins; Humans; Male; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred AKR; Pituitary Gland; Substance Withdrawal Syndrome

This study compared basal concentrations of plasma beta-endorphin/beta-lipotropin-like immunoreactivity and dexamethasone suppression of cortisol in seven chronic pain patients, seven psychiatric disorder patients, and seven normal volunteers. Pain patients and psychiatric patients showed significantly higher basal concentrations of beta-endorphin/beta-lipotropin-like immunoreactivity compared to normal volunteers. Pain patients also had significantly higher beta-endorphin/beta-lipotropin-like immunoreactivity than psychiatric patients, even though there was no significant difference in severity of depressive symptomatology as assessed by Beck and Hamilton scores. Resistance to dexamethasone occurred in 57% of pain patients. These results may indicate that biological markers for depression occur in populations of chronic pain patients, or may reflect levels of central nervous system arousal in response to stress, pain, or nonaffective phenomena.

Topics: Adult; Alcoholism; beta-Endorphin; beta-Lipotropin; Chronic Disease; Depression; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Male; Mental Disorders; Middle Aged; Mood Disorders; Pain; Radioimmunoassay; Syndrome

Topics: Alcohol Drinking; Alcoholism; Animals; beta-Endorphin; Brain; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Humans; Mice; Mice, Inbred C57BL; Rats; Receptors, Opioid; Social Environment

Blood and breath acetaldehyde levels were measured following ethanol ingestion (0.5 ml/kg) in 11 boys familially at risk for alcoholism and 11 age-matched controls. No significant differences were found between groups for acetaldehyde, objective, or subjective measures of intoxication. Previous reports of acetaldehyde as a marker of risk for alcoholism were not confirmed. Baseline behavioral state predicted response to alcohol. Children tended to have a subjective response in a direction opposite from the baseline mood state.

Topics: Acetaldehyde; Adolescent; Affect; Alcohol Drinking; Alcoholism; beta-Endorphin; Child; Child Behavior Disorders; Endorphins; Ethanol; Female; Humans; Male; Mental Recall; Risk

Alcohol addiction may induce its dependence through a mechanism involving opiate receptors and opioid peptides. For these reasons, we measured ACTH, beta-lipotropin, and beta-endorphin in the plasma and cerebrospinal fluid (CSF) of 29 alcohol addicts and compared these values with those found in 8 normal volunteers. Although no significant differences existed in peripheral concentrations of the 3 peptides, alcohol addicts had beta-endorphin levels in CSF (mean +/- SE, 29.4 +/- 4.5 fmol/ml) that were 3-fold lower than those of the controls (98.4 +/- 10.5 fmol/ml; P less than 0.001) and ACTH levels 4 times higher than control values (30.0 +/- 1.8 vs. 7.4 +/- 1.1 fmol/ml in controls; P less than 0.001), while no difference was found in beta-lipotropin levels. These results suggest that alcohol addiction is associated with a marked alteration in the CSF content of proopiocortin-related peptides which may play a role in the alcohol-seeking behavior typical of the syndrome.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; beta-Endorphin; beta-Lipotropin; Endorphins; Humans; Middle Aged

Topics: Alcoholism; beta-Endorphin; Brain; Chlordiazepoxide; Circadian Rhythm; Endorphins; Enkephalin, Methionine; Female; Fetal Blood; Humans; Liver Diseases; Male; Postoperative Period; Pregnancy

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; beta-Endorphin; Endorphins; Ethanol; Female; Humans; Mice; Mice, Inbred C57BL; Pituitary Gland; Time Factors

Topics: Alcoholism; Animals; beta-Endorphin; Brain; Corpus Striatum; Endorphins; Enkephalins; Heroin Dependence; Humans; Morphine Dependence; Opioid-Related Disorders; Pituitary Gland; Rats; Receptors, Opioid