beta-endorphin and Substance-Related-Disorders

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. Beta-endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.

Topics: Animals; Behavior, Animal; beta-Endorphin; Conditioning, Psychological; Euphoria; Humans; Reinforcement, Psychology; Substance-Related Disorders

People with a genetic predisposition for substance abuse have defects in genes for the opioid peptides and receptors. A high number of polymorphisms have been detected in the mu-opioid receptor, some of which result in pharmacological alterations. The opioid peptide proopiomelanocortin proved extraordinarily rich in mutations that often lead to severe phenotypical consequences. Prodynorphin displays a polymorphic regulation of transcription. Variants of the mu- and the delta-opioid receptor showed positive associations with opiate and/or alcohol addiction in some studies. However, these associations were weak, indicating a small contribution of the opioid system to these disorders.

Topics: Alleles; beta-Endorphin; Enkephalins; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Protein Precursors; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Substance-Related Disorders

Since the isolation of the enkephalins five yr ago, there has been an explosive increase in knowledge concerning the effects of the opiates and opioid peptides. This review deals with the interactions of opiates with the endocrine system in rat and man. The opioid peptides have been demonstrated to exert a variety of effects on pituitary hormone secretion in rat and man. In the rat, opiates stimulate growth hormone, prolactin and ACTH release and inhibit the release of the glycoprotein hormones. In man, the physiologic role of the endogenous opiates appears to be involved predominantly in ACTH and gonadotrophin regulation. Opiate effects are mainly exerted at the level of the hypothalamus but further modulating effects may occur at the pituitary and at end-organs. Opiate-induced hormonal effects appear to be mediated through dopaminergic and/or serotonergic mechanisms. Recent studies have also suggested a possible local neuromodulatory role for the opioid peptides in the control of carbohydrate metabolism and reproductive processes.

Topics: Adrenal Cortex; Animals; beta-Endorphin; beta-Lipotropin; Brain Chemistry; Carbohydrate Metabolism; Dopamine; Endorphins; Estrogens; Gonads; Growth Hormone; Humans; Hypothalamus; Morphine; Pituitary Gland; Prolactin; Rats; Serotonin; Substance-Related Disorders; Thyroid Gland; Thyrotropin

To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users.. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week.. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures.. Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

Topics: Adrenocorticotropic Hormone; Autonomic Nervous System; beta-Endorphin; Blood Pressure; Body Temperature; Cardiovascular System; Dose-Response Relationship, Drug; Double-Blind Method; Growth Hormone; Heart Rate; Humans; Hydrocortisone; Illicit Drugs; Infusions, Intravenous; N,N-Dimethyltryptamine; Placebos; Prolactin; Pupil; Substance-Related Disorders

Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer.. Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image.. Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence.. The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

Topics: Adrenocorticotropic Hormone; Adult; Affect; Anabolic Agents; Androgens; beta-Endorphin; Body Image; Case-Control Studies; Compulsive Behavior; Exercise; Humans; Hydrocortisone; Male; Middle Aged; Reinforcement, Psychology; Stress, Psychological; Substance-Related Disorders; Young Adult

Topics: Acquired Immunodeficiency Syndrome; beta-Endorphin; Demography; Environment; Health Services Needs and Demand; Hepatitis C; Hispanic or Latino; HIV Infections; Humans; Research; Substance-Related Disorders

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

Cocoa and chocolate contain the tetrahydroisoquinoline alkaloid salsolinol up to a concentration of 25 microg/g. Salsolinol is a dopaminergic active compound which binds to the D(2) receptor family, especially to the D(3) receptor with a K(i) of 0.48+/-0.021 micromol/l. It inhibits the formation of cyclic AMP and the release of beta-endorphin and ACTH in a pituitary cell system. Taking the detected concentration and the pharmacological properties into account, salsolinol seems to be one of the main psychoactive compounds present in cocoa and chocolate and might be included in chocolate addiction.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cacao; Cyclic AMP; Food Analysis; Gas Chromatography-Mass Spectrometry; Isoquinolines; Mice; Receptors, Dopamine; Stereoisomerism; Substance-Related Disorders; Tumor Cells, Cultured

Topics: Animals; Aorta, Thoracic; Cocaine; Cyclic AMP; Electric Stimulation; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Male; Mice; Muscle, Smooth; Opioid-Related Disorders; Rats; Receptors, Dopamine; Receptors, Opioid; Receptors, Serotonin; Substance-Related Disorders

Considerable evidence suggest that some responses to smoking and nicotine are mediated by forebrain beta-endorphinergic opioid mechanisms. It has also been demonstrated that nicotine stimulates rat tuberoinfundibular dopaminergic activity. Since we have proposed that interactions between mediobasohypothalamic (MBH) dopaminergic and beta-endorphinergic mechanisms have a key role in neuroendocrine integration, we investigated the effects of chronic nicotine treatment and withdrawal on: (1) MBH concentrations of proopiomelanocortin (POMC, precursor for beta-endorphin biosynthesis) mRNA; (2) MBH concentrations of tyrosine hydroxylase (TH, rate limiting enzyme in catecholamine biosynthesis) mRNA; (3) corresponding serum prolacin, corticosterone, luteinizing hormone (LH), and testosterone concentrations. POMC and TH mRNA levels were measured by RNase protection/solution hybridization assay; serum hormone levels were measured by radioimmunoassay. Adult male rats received subcutaneous injections of either nicotine or saline during the dark period of each day on an increasing frequency (1-3 injections/day) and dosage (0.4-0.5 mg nicotine/kg body weight) schedule over 4 weeks. The rats were sacrificed after 4 weeks treatment and at 1, 3, 7, 14 and 21 days withdrawal. Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated. None of the parameters were significantly different from control levels following 7 or more days of withdrawal from nicotine, except for a significant decrease of MBH POMC mRNA concentrations on day 21. Chronic daily nicotine or withdrawal did not significantly alter serum LH or testosterone concentrations. These results suggest that chronic nicotine inhibited POMC gene expression and thus, probably, biosynthesis of beta-endorphin and other opiomelanocortins. We hypothesize that suppression of forebrain beta-endorphin synthesis in response to long-term nicotine exposure produces a chronically opioid deficient condition which may play an important role in maintaining nicotine self-administration and in mediating some changes during the nicotine withdrawal syndrome.

Topics: Animals; beta-Endorphin; Brain Mapping; Gene Expression; Hypothalamus; Male; Neurosecretory Systems; Nicotine; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Immunocytochemical localization of beta-endorphin in the brains of intact and castrated male rats was conducted after the administration of high levels of androgenic-anabolic steroids (AAS; 14 daily injections of sesame oil or a cocktail of 2 mg/kg testosterone cypionate, 2 mg/kg nandrolone decanoate, and 1 mg/kg boldenone undecylenate) at doses commonly self-administered by athletes who are considered 'heavy abusers'. In normal intact oil-treated males, cytoplasmic immunoreactivity was prevalent throughout the arcuate nucleus while intense fiber tract immunoreactivity was most prevalent in the bed nucleus of the stria terminalis and the paraventricular hypothalamic nucleus. Administration of AAS significantly decreased the number of neurons exhibiting cytoplasmic immunoreactivity only in the rostral region of the arcuate nucleus. AAS treatment had no effect on beta-endorphin immunoreactivity in the middle or caudal aspects of the arcuate nucleus.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Corpus Striatum; Hypothalamus; Immunohistochemistry; Male; Rats; Rats, Sprague-Dawley; Substance-Related Disorders; Testosterone

The effect was determined of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzene- acetamide methane sulfonate (U-50,488H), a kappa opioid agonist, -induced tolerance dependence and abstinence on the levels of beta-endorphin in discrete brain regions, spinal cord, pituitary gland, plasma and peripheral tissues of male Sprague-Dawley rats. The brain regions examined were hypothalamus, hippocampus, amygdala, midbrain, corpus striatum, pons-medulla and cortex. The peripheral tissues included kidneys, spleen, adrenals and heart. Rats were made tolerant dependent on U-50,488H by intraperitoneal injections of the drug (25 mg/kg) twice a day for 4 days. Vehicle-injected rats served as controls. Rats that were labeled as tolerant dependent were injected with U-50,488H (25 mg/kg) on day 5 and killed 1 hr later, whereas those labeled as abstinent were killed without injection of the drug. Rats serving as controls were injected with the vehicle. Tolerance to the analgesic and hypothermic effects of U-50,488H developed, as evidenced by a decrease in the intensity of responses in chronic U-50,488H-treated compared with chronic vehicle-treated rats. In U-50,488H-tolerant rats, the concentration of beta-endorphin was increased in hippocampus, corpus striatum, pituitary gland, plasma, kidneys and adrenals compared with vehicle-injected controls. In U-50,488H-abstinent rats, the concentration of beta-endorphin was increased in pons-medulla and amygdala, whereas the concentration of beta-endorphin did not change in the pituitary gland, plasma and peripheral tissues. In general, chronic treatment with a kappa opioid agonist results in increases in the concentration of beta-endorphin in specific tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Brain Chemistry; Drug Tolerance; Male; Pituitary Gland; Pyrrolidines; Rats; Rats, Sprague-Dawley; Spinal Cord; Substance-Related Disorders

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

In order to establish possible different reactions between normal subjects and cocaine addicts to short term exposure to heat, thermal, cardiovascular and pituitary hormonal responses to hyperthermia in sauna were measured in 8 male cocaine addicts (studied after 14 days of abstinence) and in 8 age and weight matched normal men. Subjects sat for 30 min in a sauna room, where the temperature was 90 C and the relative humidity 10%. Physiological and hormonal parameters were measured just before and after sauna and after 30 min of rest at normal (21 C) room temperature. Significant and comparable increments in systolic and diastolic blood pressure, pulse rate and sublingual temperature were observed in the two groups at the end of sauna. All these parameters decreased to normal values after 30 min of rest at normal room temperature. Before sauna, ACTH, cortisol and beta-endorphin levels were similar in the two groups, whereas plasma prolactin concentrations were significantly higher in cocaine addicts. All examined hormones rose significantly in the normal controls at the end of sauna. All hormones, except cortisol, returned to the basal levels after 30 min at normal room temperature. In contrast, no significant hormonal responses to hyperthermia were observed at any time point in cocaine addicts. These data do not provide evidence of alterations in the cardiovascular and thermal adaptive responses to hyperthermia in cocaine abusers. On the other hand, the results show an impairment of the ACTH/cortisol, beta-endorphin and prolactin responses to hyperthermia in cocaine addicts.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; beta-Endorphin; Blood Pressure; Body Temperature; Cocaine; Fever; Heart Rate; Humans; Hydrocortisone; Male; Prolactin; Steam Bath; Substance-Related Disorders

In order to establish possible alterations in the hypothalamic pituitary-adrenal axis and in ACTH-related opioids in cocaine addicts, plasma ACTH, cortisol and beta-endorphin levels were measured throughout the day in 9 cocaine addicts [age: 27 +/- 5 years (mean +/- SE); weight: 72 +/- 6.1 kg, duration of cocaine addiction: at least 2 years] on the day of their admission to a recovery community for drug abusers (first test) and after 15 days of abstinence (second test). Nine normal controls (age: 28 +/- 6 years; weight: 73 +/- 3.2 kg) were tested only once in a similar manner. Blood samples were taken at 06:00, 08:00, 10:00, 12:00, 18:00 and 20:00 h and served for hormonal assays. Urine samples were taken from cocaine addicts at 08:00 h on the experimental day and on the following day. Results of both urine assays were positive for cocaine catabolites, indicating cocaine administration during the day before the experimental test. From the day of their admission in the community (1st experimental day), the patients were forbidden to use cocaine. For 4 days after admission, they were treated with symptomatics to attenuate withdrawal symptoms. Thereafter, the patients underwent a washout period of pharmacological treatments for 10 days before being retested (second test). Urine samples taken at 08:00 h on this second experimental day and on the next day were negative for the presence of drug catabolites. During the first test, cocaine addicts showed higher plasma ACTH, cortisol and beta-endorphin levels than normal controls at all examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Cocaine; Hormones; Humans; Hydrocortisone; Male; Substance-Related Disorders

Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks ("early") and "later," although BE levels on methadone significantly correlated with BE levels on BUP in the "early" but not the "later" phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals.

Topics: Adult; beta-Endorphin; Buprenorphine; Female; Heroin; Humans; Male; Methadone; Middle Aged; Naloxone; Radioimmunoassay; Substance Withdrawal Syndrome; Substance-Related Disorders

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Heroin Dependence; Humans; Hydrocortisone; Male; Methadone; Metyrapone; Receptors, Opioid; Reference Values; Substance-Related Disorders

The significance of beta-endorphin for drug dependence was explored by measuring the levels of beta-endorphin-immunoreactivity (beta E-IR) in plasma and parts of pituitary and brain of rats self-administering heroin or cocaine as compared to animals offered saline. Rats that had intravenously self-administrated heroin for 5 consecutive daily sessions of 6 h, and were decapitated immediately after the last session, showed a decreased concentration of beta E-IR in the anterior lobe (AL) of the pituitary while rats that had taken cocaine showed a decreased concentration of beta E-IR in the septum. Rats that had self-administrated heroin or cocaine and were decapitated 18 h after the last session, showed an increased concentration of beta E-IR in plasma and decreased concentrations in the AL of the pituitary and in specific areas of the brain limbic system, i.e. nucleus accumbens, septum, hippocampus and rostral striatum. The finding that self-administration of both the opiate heroin, inducing psychic and physical dependence, and the non-opiate cocaine, inducing psychic but not physical dependence, is accompanied by similar changes in beta E-IR concentrations particularly in limbic brain structures, and that these effects are present 18 h but not immediately after the last session, suggests that beta E and related peptides in limbic brain regions may represent a neurochemical correlate for psychic dependence on drugs.

Topics: Animals; beta-Endorphin; Brain; Cocaine; Heroin; Limbic System; Male; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Inbred Strains; Substance-Related Disorders; Tissue Distribution

Topics: Animals; Animals, Newborn; beta-Endorphin; Maternal Behavior; Neurotransmitter Agents; Nucleus Accumbens; Receptors, Neurotransmitter; Substance-Related Disorders

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

Normal responses to metyrapone were observed in most steady-state methadone maintained treatment patients. These preliminary studies suggest that in recently detoxified methadone maintained treatment patients, there may be an exaggerated response of the hypothalamic-pituitary-adrenal axis to metyrapone.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Endorphins; Female; Hormones; Humans; Hydrocortisone; Male; Methadone; Metyrapone; Substance-Related Disorders

Topics: Aging; Animals; Behavior, Animal; beta-Endorphin; Cats; Cocaine; Discrimination Learning; Dogs; Endorphins; Humans; Loperamide; Morphine; National Institutes of Health (U.S.); Norbornanes; Pupil; Rats; Reinforcement, Psychology; Substance-Related Disorders; United States

Most studies of plasma beta-endorphin concentrations in pregnant women show that these are highly elevated. This might indicate a role for opiate peptides during pregnancy and in the fetus-mother relationship. We measured plasma beta-endorphin, beta-lipotropin, and met-enkephalin concentrations in normal and drug-addicted women during pregnancy, labor, and delivery, and in their newborn infants. Peptides were measured by RIA after extraction and concentration on silica columns and separation by high pressure liquid chromatography. In both normal and drug-addicted mothers we found an increase in plasma beta-endorphin during pregnancy, without a concomitant increase in plasma beta-lipotropin or metenkephalin. Only beta-lipotropin increased dramatically in both groups at delivery, whereas beta-endorphin and met-enkephalin remained unchanged. Peptide concentrations in umbilical plasma were similar to those in peripheral plasma of the mothers. On day 1 of life plasma beta-endorphin, beta-lipotropin, and met-enkephalin concentrations in the newborn from normal mothers were higher than in nonpregnant adult subjects and gradually decreased toward normal adult values by day 5 of life. Plasma beta-endorphin, beta-lipotropin, and met-enkephalin concentrations of newborn infants of drug-addicted mothers increased dramatically on day 2 and 3 of life, up to 1000-fold the concentrations of normal adults, and remained elevated up to 40 days after birth. In conclusion, beta-endorphin, beta-lipotropin, and met-enkephalin concentrations during pregnancy are not affected by drug addiction, whereas in the newborn of drug addicted mothers concentrations of these compounds are markedly increased.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Endorphins; Enkephalin, Methionine; Female; Fetal Blood; Humans; Infant, Newborn; Labor, Obstetric; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Substance-Related Disorders