naloxone and Tremor

Repeated morphine administration increases extracellular dopamine levels in the nucleus accumbens, which results in behavioral sensitization that can be suppressed by acupuncture at Shenmen (HT7) points. The present study was conducted to investigate the effects of acupuncture at HT7 on morphine withdrawal syndrome as well as to explore the role of GABA receptors in mediating the effects of HT7 acupuncture. We induced morphine withdrawal by injecting naloxone to rats that self-administer morphine and evaluated the effects of acupuncture and/or GABA receptor antagonists on their withdrawal symptoms. Acupuncture at HT7, but not at the control point LI5, significantly decreased symptoms of morphine withdrawal. HT7 inhibition of the withdrawal syndrome was blocked by pretreatment with either the GABA(A) receptor antagonist bicuculline or the GABA(B) antagonist SCH 50911. These findings suggest that the effects of acupuncture on suppression of morphine withdrawal syndrome are mediated, at least in part, through GABA receptors.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Bicuculline; Diarrhea; GABA-A Receptor Antagonists; GABA-B Receptor Antagonists; Male; Morphine; Morphine Dependence; Morpholines; Muscle Contraction; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Receptors, GABA-B; Substance Withdrawal Syndrome; Tremor

Several lines of evidence implicate dysfunction of glutamatergic neurotransmission in opiate dependence and withdrawal. Functional antagonists of glutamatergic system, including compounds acting on both ionotropic and metabotropic glutamate receptors (group I mGlu receptor antagonists and group II mGlu receptor agonists), have been shown to decrease behavioural signs of opiate withdrawal in rodents. In the present study we analyzed an influence of group III mGlu receptor agonist, ACPT-I, on opioid withdrawal syndrome, induced by repeated morphine administration and final naloxone injection. We show, that ACPT-I significantly attenuated typical symptoms of naloxone-induced morphine withdrawal, after peripheral administration in C57BL/6J mice. These data indicate an important role of group III mGlu receptors in morphine withdrawal states and suggest that activation of group III mGlu receptors may reduce opiate withdrawal symptoms.

Topics: Analysis of Variance; Animals; Body Weight; Cyclopentanes; Disease Models, Animal; Dose-Response Relationship, Drug; Head Movements; Male; Mice; Mice, Inbred C57BL; Morphine; Morphine Dependence; Motor Activity; Naloxone; Narcotic Antagonists; Receptors, Metabotropic Glutamate; Substance Withdrawal Syndrome; Time Factors; Tremor; Tricarboxylic Acids

The purpose of the present study is to compare the capacity of opioid antagonists to elicit withdrawal jumping in mice following two acute pretreatment doses of the opioid agonist morphine. Antagonists that precipitate vigorous withdrawal jumping across both morphine treatment doses are hypothesized to be strong inverse agonists at the mu-opioid receptor, whereas antagonists that elicit withdrawal jumping in mice treated with the high but not the low dose of morphine are hypothesized to be weak inverse agonists. Male, Swiss-Webster mice (15-30 g) were acutely treated with 56 or 180 mg kg(-1) morphine 4 h prior to injection with naloxone, naltrexone, diprenorphine, nalorphine, or naloxonazine. Vertical jumping, paw tremors, and weight loss were recorded. Naloxone, naltrexone, and diprenorphine produced withdrawal jumping after 56 and 180 mg kg(-1)morphine pretreatment. Nalorphine and naloxonazine produced moderate withdrawal jumping after 180 mg kg(-1) morphine pretreatment, but failed to elicit significant withdrawal jumping after 56 mg kg(-1) morphine pretreatment. Nalorphine and naloxonazine blocked the withdrawal jumping produced by naloxone. All antagonists produced paw tremors and weight loss although these effects were generally not dose-dependent. Taken together, these findings reveal a rank order of negative intrinsic efficacy for these opioid antagonists as follows: naloxone=naltrexone> or =diprenorphine>nalorphine=naloxonazine. Furthermore, the observation that nalorphine and naloxonazine blocked the naloxone-induced withdrawal jumping provides additional evidence that nalorphine and naloxonazine are weaker inverse agonists than naloxone.

Topics: Animals; Behavior, Animal; Body Weight; Brain; Diprenorphine; Dose-Response Relationship, Drug; Male; Mice; Morphine; Morphine Dependence; Naloxone; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome; Tremor

Much evidence supports the hypothesis that A2A adenosine receptors play an important role in the expression of morphine withdrawal and that the dopaminergic system might also be involved. We have evaluated morphine withdrawal signs in wild-type and A2A receptor knockout mice and shown a significant enhancement in some withdrawal signs in the knockout mice. In addition, micro -opioid and dopamine D2 receptor autoradiography, as well as micro -opioid receptor-stimulated guanylyl 5'-[gamma-[35S]thio]-triphosphate ([35S]GTPgammaS) autoradiography was carried out in brain sections of withdrawn wild-type and knockout mice. No significant changes in D2 and micro -opioid receptor binding were observed in any of the brain regions analysed. However, a significant increase in the level of micro receptor-stimulated [35S]GTPgammaS binding was observed in the nucleus accumbens of withdrawn knockout mice. These data indicate that the A2A receptor plays a role in opioid withdrawal related to functional receptor activation.

Topics: Analysis of Variance; Animals; Autoradiography; Behavior, Animal; Binding Sites; Brain; Densitometry; Diarrhea; Dose-Response Relationship, Drug; Drug Interactions; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Male; Mice; Mice, Knockout; Morphine; Motor Activity; Naloxone; Narcotic Antagonists; Raclopride; Receptor, Adenosine A2A; Receptors, Opioid, mu; Substance Withdrawal Syndrome; Sulfur Isotopes; Tremor; Tritium; Urine; Weight Loss

An increasing and serious heroin overdose problem in Oslo has mandated the increasing out-of-hospital use of naloxone administered by paramedics. The aim of this study was to determine the frequencies and characteristics of adverse events related to this out-of-hospital administration by paramedics.. A one-year prospective observational study from February 1998 to January 1999 was performed in patients suspected to be acutely overdosed by an opioid. A total of 1192 episodes treated with naloxone administered by the Emergency Medical Service system in Oslo, were included. The main outcome variable was adverse events observed immediately after the administration of naloxone.. The mean age of patients included was 32.6 years, and 77% were men. Adverse events suspected to be related to naloxone treatment were reported in 45% of episodes. The most common adverse events were related to opioid withdrawal (33%) such as gastrointestinal disorders, aggressiveness, tachycardia, shivering, sweating and tremor. Cases of confusion/restlessness (32%) might be related either to opioid withdrawal or to the effect of the heroin in combination with other drugs. Headache and seizures (25%) were probably related to hypoxia. Most events were non-serious. In three episodes (0.3%) the patients were hospitalized because of adverse events.. Although adverse events were common among patients treated for opioid overdose in an out-of-hospital setting, serious complications were rare. Out-of-hospital naloxone treatment by paramedics seems to save several lives a year without a high risk of serious complications.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Confusion; Drug Overdose; Emergency Medical Services; Female; Headache; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Nausea; Norway; Prospective Studies; Seizures; Substance-Related Disorders; Tachycardia; Tremor; Vomiting

Contexts associated with drug use can acquire secondary reinforcing properties. Furthermore, context-specific withdrawal has been observed to reflect a relatively long-lasting learned response. The aim of this study was to evaluate the effect of the environment paired with morphine after 15 days of abstinence. In the first experiment, isolated male mice received saline or morphine either in their home cage or in the distinctive environment, performing two agonistic encounters in the distinctive environment during spontaneous withdrawal. Similar groups were assigned but without aggression encounters during withdrawal. In the second experiment, animals received saline or morphine as previously described but suffered two naloxone-induced withdrawals during agonistic encounters. In all cases, after the second withdrawal, animals were drug-free during 15 days and then an aggression test took place in the distinctive environment. Results show that experience of aggression during this spontaneous withdrawal causes an increase in the level of aggression exhibited when animals are drug free, in comparison with others in which this experience does not exist. Environment associated with morphine administration decreases conditioned physical signs of withdrawal and to a smaller extent aggression. It could be suggested that environment associated with morphine administration decreases the abnormal behaviors exhibited in postdependent mice.

Topics: Agonistic Behavior; Animals; Convalescence; Environment; Housing, Animal; Male; Mice; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Reward; Single-Blind Method; Substance Withdrawal Syndrome; Tremor

Between 1987 and 1997, we chemically immobilized 597 wild sea otters (Enhydra lutris) in Alaska for the collection of biological samples or for surgical instrumentation. One drug-related sea otter fatality occurred during this time. Fentanyl in combination with diazepam produced consistent, smooth inductions with minimal need for supplemental anesthetics during procedures lasting 30-40 min. Antagonism with naltrexone or naloxone was rapid and complete, although we observed narcotic recycling in sea otters treated with naloxone. For surgical procedures, we recommend a fentanyl target dose of 0.33 mg/kg of body mass and diazepam at 0.11 mg/kg. For nonsurgical biological sample collection procedures, we recommend fentanyl at 0.22 mg/kg and diazepam at 0.07 mg/kg. We advise the use of the opioid antagonist naltrexone at a ratio of 2:1 to the total fentanyl administered during processing.

Topics: Anesthesia; Anesthetics, Combined; Anesthetics, Intravenous; Animals; Azaperone; Body Temperature; Diazepam; Female; Fentanyl; Heart Rate; Hypnotics and Sedatives; Immobilization; Logistic Models; Male; Naloxone; Naltrexone; Narcotic Antagonists; Otters; Respiration; Seizures; Time Factors; Tremor

The abuse of benzodiazepines by narcotic addicts has been well documented. However, the pharmacological basis of this abuse is not clear. In this study the effects of different benzodiazepines (flunitrazepam: 0.5, 1 and 2 mg/kg; nitrazepam: 0.5, 1, 2.5, 5 and 10 mg/kg; diazepam: 0.5, 1, 2.5, 5 and 10 mg/kg; chlordiazepoxide: 0.5, 1, 2.5, 5 and 10 mg/kg; and triazolam: 0.5, 1 and 2 mg/kg) on the morphine withdrawal syndrome in mice have been compared. Drugs were administered 30 min before naloxone-induced withdrawal. All benzodiazepines tested induced similar changes in some of the signs of morphine abstinence: decreased jumping behavior and increased wet dog shake frequency. Jumping behavior was particularly decreased by triazolam and wet dog shakes were mainly increased by flunitrazepam and nitrazepam. Forepaw treading was reduced by flunitrazepam, diazepam and triazolam, increased by nitrazepam and not changed by chlordiazepoxide. Tremor was effectively reduced by diazepam but less reliably by the other benzodiazepines. Teeth chattering was reduced by flunitrazepam and diazepam. These results indicate that benzodiazepines can interfere with the expression of the morphine withdrawal syndrome.

Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Benzodiazepines; Male; Mice; Morphine Dependence; Naloxone; Regression Analysis; Substance Withdrawal Syndrome; Tremor

Peripheral glucose administration enhances memory in rodents and humans. Recent findings suggest that glucose may affect behavior, in part, by augmenting central cholinergic functions and by attenuating central opiate functions. The present experiments examined interactions between an opiate antagonist, naloxone, and cholinergic agents to determine whether the effects would parallel those found with glucose. Three behavioral measures were assessed: tremors, hyperactivity, and spontaneous alternation. Naloxone (1 mg/kg) significantly augmented tremors elicited by physostigmine (0.3 mg/kg). Naloxone (1 mg/kg) also attenuated increases in locomotor activity and impairments in spontaneous alternation performance elicited by scopolamine (1 and 3 mg/kg for activity and alternation measures, respectively). Thus, across three diverse measures, naloxone produced effects similar to those previously reported for glucose. These findings are consistent with the hypothesis that release of cholinergic activity from opiate inhibition may contribute to glucose effects on behavior.

Topics: Animals; Behavior, Animal; Female; Glucose; Mice; Mice, Inbred ICR; Morphine; Motor Activity; Naloxone; Parasympatholytics; Parasympathomimetics; Physostigmine; Psychomotor Performance; Scopolamine; Tremor

1. Doses of buprenorphine (0.01, 0.1, 0.5, 1, 5, 10 and 50 mg/kg) were administered to determine buprenorphine's ability to precipitate abstinence symptoms in morphine-dependent mice. 2. When buprenorphine was administered in the fourth day of morphine addiction, the results demonstrate that the administration of the partial agonist opioid produce a bell-shaped dose-response curve. 3. The highest dose (50 mg/kg) was partially inactive while lower doses causing similar percentage than group treated with naloxone with respect to the appearance of the most of the symptoms of abstinence studied (diarrhoea, tremor, shaking-"wet dog shakes"-, jumping and weight loss). 4. Our findings demonstrate the bell-shaped response curve of the antagonist effects of buprenorphine.

Topics: Animals; Behavior, Animal; Buprenorphine; Diarrhea; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred Strains; Morphine Dependence; Naloxone; Substance Withdrawal Syndrome; Tremor

Because of anecdotal reports in which ibogaine eliminates opioid withdrawal symptoms in humans, we studied this phenomenon in the rat model. Ibogaine (5, 10, 20 and 40 mg kg-1, s.c.) was administered 15 min before naloxone (0.5 mg kg-1, s.c.) in morphine dependent rats (3 days after the s.c. implantation of a 75 mg morphine pellet). Of the 12 withdrawal signs scored, the only significant changes observed after ibogaine (compared with vehicle control) was a decrease in grooming (10 mg kg-1) and an increase in teeth chatter (5 mg kg-1). In spite of ibogaine's apparent interaction with several neurotransmitter receptor systems, it does not alleviate opioid withdrawal in this animal model at non-tremorigenic (5 and 10 mg kg-1) or tremorigenic (20 and 40 mg kg-1) doses.

Topics: Animals; Behavior, Animal; Grooming; Ibogaine; Male; Morphine Dependence; Naloxone; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome; Tremor

Effects of the opioid antagonist naloxone (10 mg/kg) and its interaction with anticholinergic (scopolamine) and dopaminergic (bromocriptine) agents against tremorine-induced tremors was studied. Naloxone (10 mg/kg) per se gave significant protection and significantly potentiated the protective effect of scopolamine against tremorine-induced tremors at 5 min only. When naloxone and subeffective dose of bromocriptine (2 mg/kg) were administered simultaneously, instead of protection, an enhancement of tremorogenic activity was seen. Although the exact mechanism of this drug interaction is far from clear, a multireceptor involvement (i.e. opioid, dopaminergic and cholinergic type) in the modulation of tremorine-induced tremors in mice has been speculated.

Topics: Animals; Bromocriptine; Male; Mice; Naloxone; Scopolamine; Tremor; Tremorine

Oxotremorine-induced tremor activity in mice was suppressed by pretreatment with either L-dopa or atropine. Additional pretreatment with the opiate receptor blocker naloxone significantly potentiated the antitremor effect of L-dopa but not that of atropine. These findings indicate a selectivity of drug interaction between naloxone and L-dopa.

Topics: Animals; Atropine; Drug Synergism; Levodopa; Male; Mice; Mice, Inbred ICR; Naloxone; Oxotremorine; Time Factors; Tremor

Although the morphine withdrawal syndrome has been well described in the rat, a syndrome having similar characteristics has not been demonstrated following chronic methadone treatment. In this study we describe the behavioral effects produced by naloxone (4 mg/kg sc) following 72 hours of continuous iv infusion of methadone, (12.2 micrograms/kg/min), morphine (12.2 to 97.9 micrograms/kg/min) or saline. The cessation of methadone or morphine but not saline treatment followed by naloxone resulted in graded signs including wet dog shakes, escape attempts, self-stimulation and body weight loss and quantal signs including diarrhea, ear blanching, exophthalmos, ptosis, tachypnea and teeth chattering. These results indicate that this mode of methadone administration produces physical dependence characterized by a morphine-like withdrawal syndrome in the rat.

Topics: Animals; Behavior, Animal; Body Weight; Escape Reaction; Humans; Male; Methadone; Morphine; Motor Activity; Naloxone; Rats; Rats, Inbred Strains; Self Stimulation; Substance-Related Disorders; Tremor

Naloxone in doses up to 2 mg/kg and beta-endorphin in doses up to 1 mg/kg had no suppressive effect on pressure-induced tremor or cortical EEG activity in the guinea pig. The lack of effect of either naloxone or beta-endorphin on the HPNS provides evidence that opiate receptor mechanisms are not significantly involved in this syndrome.

Topics: Animals; Atmosphere Exposure Chambers; beta-Endorphin; Endorphins; Guinea Pigs; Male; Naloxone; Pressure; Receptors, Opioid; Tremor

Pretreatment with the catecholamine precursor L-DOPA but not the narcotic antagonist naloxone suppressed the tremorigenic effect of oxotremorine in mice. However, when animals were pretreated with both L-DOPA and several different doses of naloxone, there was a dose-related potentiation of the antitremor effect of L-DOPA. Naloxone also produced dose-dependent potentiation of the antitremor activity of lower doses of L-DOPA in the presence of the peripheral decarboxylase inhibitor carbidopa. These findings suggest a possible therapeutic application for naloxone in treatment of dopamine dysfunction disorders.

Topics: Animals; Carbidopa; Dose-Response Relationship, Drug; Drug Synergism; Levodopa; Male; Mice; Mice, Inbred ICR; Naloxone; Oxotremorine; Tremor

Topics: Animals; Female; Injections, Intraventricular; Morphine; MSH Release-Inhibiting Hormone; Muscle Rigidity; Muscle Tonus; Naloxone; Naltrexone; Rats; Rats, Inbred Strains; Time Factors; Tremor; Tremorine

Topics: Blood Pressure; Body Temperature; Heart Rate; Humans; Male; Naloxone; Pupil; Respiration; Time Factors; Tremor

A procedure for administering naloxone to narcotic-dependent individuals and a technique for quantitating the ensuing acute withdrawal syndrome have been developed to assess the degree of physical dependence. Successive injections of increasing doses of naloxone produce a controlled increase in severity of withdrawal signs and symptoms as measured by a subjective and an objective assessment battery. There is good agreement between the subjective and objective assessments and a global reting of withdrawal severity. The objective measures are, however, most sensitive and produce a withdrawal syndrome score related to the duration of the current cycle of drug abuse. Hand tremor, trapezius electromyogram and heart rate are the most sensitive signs of withdrawal and can be used in combination to form the basis of a simplified and shortened antagonist assessment test for physical dependence.

Topics: Blood Pressure; Electromyography; Female; Heart Rate; Heroin Dependence; Humans; Infusions, Parenteral; Male; Naloxone; Respiration; Self-Assessment; Skin Temperature; Substance Withdrawal Syndrome; Time Factors; Tremor

Intraventricular administration of a peptide from ovine pituitaries whose structure is identical to the 61-91 C-terminal portion of beta-lipotropic hormone (61-91 beta-LPH) induced catalepsy, muscular hypertonus and analgesia in rats. Naloxone inhibited both the analgesic and cataleptic effects. 1-dihydroxyphenylalanine (1-DOPA) completely prevented the cataleptic effect. The cataleptic effect of 61-91 beta-LPH was potentiated by 1-5-hydroxytryptophan (5-HTP).

Topics: 5-Hydroxytryptophan; Animals; beta-Lipotropin; Catalepsy; Catatonia; Dose-Response Relationship, Drug; Humans; Levodopa; Naloxone; Rats; Sheep; Tremor

The influence of clonidine on the naloxone-induced withdrawal signs, escape attempts and precipitated shakes, was studied in morphine-dependent rats. Clonidine injected i.p. or intraventricularly (i. vent.) inhibited precipitated shakes and potentiated escape attempts induced by naloxone in morphine-dependent rats. Under pentobarbital anesthesia, precipitated shakes and ice water-induced wet shakes were inhibited by clonidine and norepinephrine. Clonidine injected i. vent. reduced body temperatures in morphine-dependent rats but not in placebo pellet-implanted rats. We suggest that clonidine modulates morphine withdrawal signs by potentiating the behavior associated with heat dissipation (escape attempts) and inhibiting the behavior associated with heat gain mechanisms (precipitated shakes). These effects may occur via stimulation of central noradrenergic mechanisms.

Topics: Anesthesia; Animals; Body Temperature; Cerebral Ventricles; Clonidine; Escape Reaction; Exophthalmos; Humans; Injections; Male; Morphine Dependence; Naloxone; Norepinephrine; Pentobarbital; Piloerection; Rats; Substance Withdrawal Syndrome; Time Factors; Tremor

Topics: Analgesics; Animals; Codeine; Dextropropoxyphene; Dose-Response Relationship, Drug; Drug Interactions; Hot Temperature; Levorphanol; Male; Meperidine; Methadone; Mice; Mice, Inbred Strains; Naloxone; Pentazocine; Physical Stimulation; Reaction Time; Seizures; Time Factors; Tremor