nalorphine and Substance-Withdrawal-Syndrome

Topics: Administration, Oral; Apgar Score; Birth Weight; Child; Child Care; Female; Gestational Age; Heroin Dependence; Humans; Infant, Newborn; Levallorphan; Maternal-Fetal Exchange; Methadone; Nalorphine; Naloxone; Phenobarbital; Poisoning; Pregnancy; Substance Withdrawal Syndrome; Tablets

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Codeine; Drug Tolerance; Guinea Pigs; Half-Life; Haplorhini; Humans; Ileum; In Vitro Techniques; Meperidine; Mice; Molecular Conformation; Morphinans; Nalorphine; Narcotic Antagonists; Pentazocine; Rats; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; Tail

Topics: Animals; Behavior, Animal; Cyclazocine; Cyclopropanes; Dose-Response Relationship, Drug; Facial Expression; Handling, Psychological; Haplorhini; Humans; Morphinans; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Species Specificity; Structure-Activity Relationship; Substance Withdrawal Syndrome; Thebaine; Time Factors

Topics: Analysis of Variance; Cyclazocine; Drug Evaluation; Humans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pupil; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors

Topics: Animals; Chlorpromazine; Codeine; Cyclazocine; Drug Combinations; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Lysergic Acid Diethylamide; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pentobarbital; Rats; Receptors, Drug; Species Specificity; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

Topics: Animals; Avoidance Learning; Behavior, Animal; Chlorpromazine; Columbidae; Conditioning, Operant; Cyclazocine; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Drug Tolerance; Humans; Methadone; Morphine; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Pentazocine; Rats; Reinforcement Schedule; Substance Withdrawal Syndrome

Topics: Analgesics; Aspirin; Caffeine; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Female; Headache; Humans; Indoles; Isoquinolines; Meperidine; Morphine; Nalorphine; Narcotics; Pain; Periodontal Diseases; Phenacetin; Placebos; Postoperative Care; Pregnancy; Puerperal Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

A randomized and blind experimental design was used to study the effects of naloxone and nalorphine on the development of morphine dependence in monkeys. The results suggest: (a) that significant dose-related differences existed for combined numbers of withdrawal symptoms times frequency of occurrences; (b) that naloxone and nalorphine were qualitatively similar; (c) antagonists are more effective as dependence develops; (d) naloxone is approximately 10 times more potent than nalorphine, and (e) vomiting was the only withdrawal sign with which ED50s could be calculated. Dependence on morphine still increases up to 9 months after the commonly accepted 90-day stabilization period as measured by the ED50 for vomiting for naloxone.

Topics: Animals; Dose-Response Relationship, Drug; Female; Haplorhini; Humans; Macaca mulatta; Male; Morphine; Morphine Dependence; Nalorphine; Naloxone; Substance Withdrawal Syndrome; Vomiting

Topics: Analysis of Variance; Codeine; Cyclazocine; Dextropropoxyphene; Dose-Response Relationship, Drug; Emotions; Humans; Levallorphan; Lysergic Acid Diethylamide; Morphine Dependence; Nalbuphine; Nalorphine; Narcotic Antagonists; Pentazocine; Placebos; Substance Withdrawal Syndrome; Surveys and Questionnaires

Topics: Animals; Aspirin; Brain; Cyclazocine; Drug Tolerance; Fenclonine; Humans; Levorphanol; Male; Methadone; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Pargyline; Pentazocine; Phenylalanine; Physostigmine; Placebos; Serotonin; Substance Withdrawal Syndrome

Topics: Adult; Aged; Amines; Amino Alcohols; Analgesics; Benzyl Compounds; Blood Pressure; Body Temperature; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Nalorphine; Pain; Pulse; Pyrroles; Respiration; Substance Withdrawal Syndrome

Topics: Analgesics; Aspirin; Caffeine; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Female; Headache; Humans; Indoles; Isoquinolines; Meperidine; Morphine; Nalorphine; Narcotics; Pain; Periodontal Diseases; Phenacetin; Placebos; Postoperative Care; Pregnancy; Puerperal Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Analgesics; Behavior; Bridged-Ring Compounds; Drug Antagonism; Furans; Humans; Ketones; Levallorphan; Morphine; Nalorphine; Narcotic Antagonists; Phenanthrenes; Placebos; Psychological Tests; Pupil; Substance Withdrawal Syndrome

Topics: Amphetamine; Analgesics; Barbiturates; Cannabis; Clinical Trials as Topic; Cocaine; Cyclazocine; Drug Tolerance; Euphoria; Humans; Morphine; Nalorphine; Narcotic Antagonists; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Clinical Trials as Topic; Drug Tolerance; Humans; Morphine; Nalorphine; Narcotic Antagonists; Placebos; Substance Withdrawal Syndrome; Substance-Related Disorders

The aim of this study was to eliminate endogenous stores of histamine before inducing the precipitated withdrawal syndrome. Results demonstrate that histamine plays a role in the emergence of some of the symptoms which characterize the precipitated abstinence syndrome in morphine-dependent dogs. Morphine-dependent dogs receiving 0.5 mg/kg n-allyl-normorphine exhibit the precipitated abstinence syndrome. Injection of compound 48/80, 0.5 mg/kg, a potent histamine liberator, produced, on the other hand, typical signs of the abstinence syndrome. A second injection of this compound 24 hours later, however, failed to induce these signs. An injection of n-allyl-normorphine also failed to induce these signs in dogs pretreated with compound 48/80 despite the fact that the dogs were still on their morphine regime. Control experiments on naive animals showed that injection of 0.5 mg/kg n-allyl-normorphine failed to produce signs of the abstinence syndrome. Injection of compound 48/80, a potent histamine liberator, on the other hand, did produce the typical signs of the abstinence syndrome. Animals pretreated with n-allyl-normorphine followed by compound 48/80 responded similarly to animals treated with compound 48/80 alone.

Topics: Animals; Dogs; Female; Humans; Male; Morphine Dependence; Nalorphine; p-Methoxy-N-methylphenethylamine; Substance Withdrawal Syndrome

Topics: Animals; Body Weight; Diarrhea; Female; Humans; Intestines; Morphine Dependence; Nalorphine; Naltrexone; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome

Series of N-(cyclopropylmethyl) (P series) or N-(cyclobutylmethyl) (B series) 3-methoxy (1) or 3-hydroxy (2) morphinan-6-ones with hydrogen (a), methyl (b), or ethyl (c) groups in the 8 beta position were converted to the 6-methylene compounds 3 or 4 by reaction with Ph3P = CH2. One member of this new series, N-(cyclobutylmethyl)-8 beta-methyl-6-methylenemorphinan-3-ol (4Bb), had potent mixed agonist-narcotic antagonist properties and, in contrast to the previously studied 6-oxo compound 2Bb, did not substitute for morphine in dependent rats or monkeys.

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Haplorhini; Humans; Mice; Morphinans; Morphine Dependence; Narcotic Antagonists; Rats; Reaction Time; Substance Withdrawal Syndrome

The effects of morphine, nalorphine and morphine withdrawal on intracerebroventricular kainic acid (0.1 and 0.2 micrometers) lethal toxicity were examined. Morphine (40 mg/kg) potentiated the lethal effect of a low (0.1 micrometer) but not that of a higher dose (0.2 micrometer) of kainic acid. Nalorphine (20 mg/kg) did not affect the toxic action of kainic acid. The mice during morphine withdrawal were very sensitive to the lethal effects of both doses of the amino acid. Kainic acid toxicity seems to be closely related to the functional state of the opiate system. Moreover, it seems that in tolerant animals a supersensitivity of glutamatergic receptors is likely to occur.

Topics: Animals; Drug Synergism; Humans; Kainic Acid; Male; Mice; Morphine; Nalorphine; Pyrrolidines; Substance Withdrawal Syndrome

A series of 8-alkyl-3-methoxy-17-methylmorphinan-6-ones (3C) and -isomorphinan-6-ones (3T) were prepared by conjugate addition of lithium dialkylcuprates to the corresponding 7,8-didehydro-6-ones 2C and 2T. These 17-methyl compounds were potent analgesics and were converted to mixed narcotic agonists-antagonists 7-10, by replacement of the 17-methyl groups with cycloalkylmethyl moieties. The 8 substituent modified the type of activity observed. One of these compounds, 17-(cyclobutylmethyl)-3-hydroxy-8 beta-methylmorphinan-6-one (10Ca), had an agonist-antagonist ratio of 0.1. Compound 10Ca did not support or cause dependence in rats. This compound, however, appeared to be a typical narcotic agent in morphine-dependent monkeys.

Topics: Acetates; Analgesics; Animals; Haplorhini; Humans; Mice; Morphinans; Morphine Dependence; Narcotic Antagonists; Rats; Reaction Time; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders

3,6-Dimethoxy-7 beta, 17-dimethyl-4-hydroxy-5,6,8,14-tetradehydromorphinan (2) was converted to the 4-deoxy compound 4 and hydrolyzed to a mixture of the B/C-cis (C series) and B/C-trans (T series) isomers of 7,8-didehydromorphinan-6-one, 5. Hydrogenation of the separated isomers gave 7-methyl-6-oxo derivatives 6a. 7,8-Dimethyl-(6b) or 7-methyl-8-ethylmorphinan-6-one (6c) was prepared by reaction of 5 with lithium organocuprates. The analgesic N-methyl compounds 6 were converted to 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 10--13. Some of these compounds had mixed profiles of narcotic agonist-antagonist effects. Studies with drug-dependent monkeys indicated that several of these compounds with an analgesic-antagonist ratio of less than 0.4 substitute for morphine.

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Humans; Morphinans; Morphine Dependence; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Animals; Central Nervous System Depressants; Codeine; Drug Evaluation, Preclinical; Haplorhini; Humans; Macaca; Macaca mulatta; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Self Administration; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The aim of the present study was to investigate the effects of acute and chronic administration of morphine upon the pituitary-adrenal activity and adrenal catecholamines in rats and cats, two animal species with very different behavioural patterns of response to the opiate. Acute administration of the drug induced in both animal species an activation of the pituitary-adrenal system. Chronic administration of morphine to cats and rats induced a depression in the pituitary-adrenal function. No significant changes in the adrenal levels of catecholamines were observed in rats treated chronically with the drug. However, in the cat, the effects of morphine on adrenomedullary function seemed to depend on the stage of morphine treatment. The behavioural patterns of response in both animal species during chronic administration of the opiate, as well as the effects of induced withdrawal with nalorphine (an antagonist of morphine), indicated that dependence on morphine had developed, not only in the rats, but also in the cats. Acute morphine administration had a sedative effect, while in the cats the opiate produced a species-specific manic response characterized by hyperexcitement and aggressive behavior.

Topics: Adrenal Glands; Animals; Catecholamines; Cats; Female; Humans; Hydrocortisone; Male; Morphine; Nalorphine; Pituitary-Adrenal System; Rats; Species Specificity; Substance Withdrawal Syndrome

Intracerebral administration of copper sulfate potentiated morphine analgesia in morphine-tolerant and -dependent mice, but copper failed to affect other abstinence signs. When abstinence was precipitated with a partial antagonist, nalorphine, stereotyped jumping was not inhibited by either calcium or copper. These modifications of narcotic effects by copper were produced without alterations in the brain disposition of morphine. Total radioactivity in the brain following radioactive naloxone administration was also not altered.

Topics: Analgesia; Animals; Calcium; Cations, Divalent; Copper; Humans; Male; Mice; Morphine; Morphine Dependence; Nalorphine; Naloxone; Substance Withdrawal Syndrome

Rats with lateral hypothalamic self-stimulation were treated chronically with morphine (30 injections in the course of 15 days) in doses increasing stepwise from 20 to 120 mg/kg per injection. Morphine facilitated self-stimulation from the 9th injection. Both short-term abstinence (16-18 hours) and cessation of the narcotic resulted in inhibition of the response. Full suppression of self-stimulation occurred under the administration of nalorphine, morphine antagonist, in a dose of 5 mg/kg.

Topics: Animals; Depression, Chemical; Electric Stimulation; Humans; Hypothalamus; Male; Morphine; Nalorphine; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome; Substance-Related Disorders

The effect of nalorphine on eliciting symptoms of either alcohol or narcotic withdrawal was studied. Five male alcoholics were challenged with nalorphine and saline, both while sober and during alcohol ingestion. After nalorphine, pulse rate decreased in patients when sober, but increased when they were ingesting alcohol. Nalorphine administration resulted, during alcohol ingestion, but not in the sober state, in lacrimation, a symptom of narcotic withdrawal, in one patient, and in the following symptoms of alcohol or narcotic withdrawal in one or more patients: weakness, anorexia, insomnia, disorientation, and tremor. These findings suggest that morphine-like alkaloids play a role in the mediation of alcohol withdrawal symptoms.

Topics: Adult; Alcoholism; Humans; Male; Middle Aged; Nalorphine; Substance Withdrawal Syndrome; Tears

Topics: Analgesics, Opioid; Animals; Benzimidazoles; Cerebral Cortex; Conditioning, Classical; Conditioning, Operant; Conditioning, Psychological; Cues; Diethylamines; Drug Tolerance; Emotions; Environment; Euphoria; Humans; Morphine; Morphine Dependence; Nalorphine; Reinforcement, Psychology; Retrospective Studies; Substance Withdrawal Syndrome; Substance-Related Disorders

Apomorphine pretreatment potentiated the analgesic effect of morphine in a dose-dependent manner both in rats and in mice measured by five different tests (writhing, hot plate, inflamed foot, tail-pinch and tail-flick procedures). Furthermore, apomorphine augmented the antinociceptive activity of morphine in tolerant animals as well. In morphine dependent mice the nalorphine precipitated jumping--a withdrawal symptom--was found inhibited by apomorphine treatment. The results are discussed in the light of the numerous but contradictory data available in the literature.

Topics: Analgesics, Opioid; Animals; Apomorphine; Drug Synergism; Drug Tolerance; Female; Humans; Male; Mice; Morphine; Nalorphine; Rats; Rats, Inbred Strains; Reaction Time; Substance Withdrawal Syndrome; Time Factors

Topics: Animals; Clonidine; Cyproheptadine; Humans; Male; Morphine Dependence; Nalorphine; Rats; Substance Withdrawal Syndrome; Time Factors

A series of 53 1-phenyl-6-azabicyclo[3.2.1]octanes (1) has been tested for their analgetic and narcotic antagonist activities. Structure-activity relationships were investigated by varying the structural parameters. The most interesting compound in this series, the 1-(3-hydroxphenyl)-6,7-dimethyl derivative 8, shows the profile of a well-balanced antagonist-analgesic agent with a very mild physical dependence capacity. The absolute stereochemistry of its active enantiomer [(+)8] was established by the x-ray study and the chemical transformation to the phenylmorphan [(+)-II]. (+)-8 was stereochemically correlated also with the active enantiomer of the 7-demethyl derivatives [(+)-7] by chemical transformation and CD measurement. Certain structural and stereochemical correlations between these compounds (7 and 8) and other known antagonist-analgetics are discussed.

Topics: Analgesics; Animals; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Haplorhini; Humans; Lethal Dose 50; Macaca mulatta; Molecular Conformation; Nalorphine; Narcotic Antagonists; Rabbits; Stereoisomerism; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; X-Ray Diffraction

Topics: Analgesia; Animals; Body Weight; Drug Interactions; Drug Tolerance; Humans; Male; Morphine; Nalorphine; Naloxone; Rats; Reaction Time; Receptors, Opioid; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Rats previously trained to a fixed-interval schedule (FI 2 min) were treated twice daily with saline or morphine hydrochloride (final dose 40 mg/kg i.p.) for 44 days. On day 45 an abstinence state was induced by withdrawing morphine or by giving nalorphine (1 mg/kg i.p.). Operant behavior was recorded on alternate days during the period of chronic treatment and during the withdrawal phase (21 days). It was found that the number of lever presses decreased significantly during the first days of morphine administration but increased later over the control values. The quarter-life was not changed during this period. Morphine withdrawal and nalorphine treatment both caused a further increase in lever presses that lasted about 11 days. Again quarter-life was not changed. These results indicate that the effects of morphine on FI behavior in rats not only undergo tolerance but are actually reversed during the chronic treatment. The data obtained during the withdrawal phase are discussed in relation to the secondary abstinence syndrome described by Martin et al. (1963).

Topics: Animals; Body Weight; Conditioning, Operant; Drug Tolerance; Humans; Male; Morphine; Morphine Dependence; Nalorphine; Rats; Reinforcement Schedule; Substance Withdrawal Syndrome; Time Factors

In morphine-dependent rats the withdrawal precipitating properties of various morphine antagonists and partial agonists were studied by quantitatively evaluating a variety of different withdrawal signs. A comparison of the dose response curves of the various substances obtained for the different signs revealed marked differences in respect to the lowest effective doses (EDs) necessary to precipitate the withdrawal signs as well as in the maximum frequencies of the signs induced. The "pure" antagonist, naloxone, which was judged very potent according to the ED, precipitated the lowest levels of jumping, whereas certain partial agonists of the benzomorphane type, which were less potent according to the ED, induced very high levels of this sign. These latter compounds, however, failed to precipitate "complete" withdrawal, as evidenced by the nearly complete absence of some of the withdrawal signs. The jumping precipitating potency of the antagonists as judged from the ED was found to be highly correlated to the stereospecific binding of these substances to rat brain homogenate. On the other hand, the ability of the substances to precipitate high levels of jumping was seen to increase, at least within a certain range, with increasing degree of agonistic properties, as indicated by the ratio of stereospecific binding in the presence and absence of sodium.

Topics: Benzomorphans; Binding Sites; Brain; Humans; Levallorphan; Morphine Dependence; Nalorphine; Naloxone; Naltrexone; Narcotic Antagonists; Pentazocine; Receptors, Drug; Sodium; Stereoisomerism; Subcellular Fractions; Substance Withdrawal Syndrome

A series of morphine-like and nalorphine-like drugs were studied in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. In the nondependent dog, three profiles of activity were found which could be utilized to distinguish between morphine, WIN 35, 197-2 and cyclazocine. Propiram, a prototypic partial agonist of the morphine type, produced morphine-like effects in nondependent dogs and both precipitated and suppressed abstinence in cyclazocine-dependent dogs as was needed to precipitate abstinence in morphine-dependent dogs. WIN 35, 197-2, a strong agonist in the guinea-pig ileum which has been shown to be resistant to antagonism by naloxone, neither precipitated nor suppressed morphine abstinence but suppressed cyclazocine abstinence. In the nondependent dog, it depressed the flexor reflex but not skin twitch reflex. Cyclazocine altered reflex activity much like WIN 35, 197-2 but produced tachycardia, tachypnea, mydriasis and canine delirum. The morphine and cyclazocine precipitated and withdrawal abstinence syndromes were qualitatively different. Twenty times as much naltrexone was needed to precipitate abstinence in morphine-dependent dogs. Nalorphine both precipitated and suppressed cyclazocine abstinence and appeared to be a partial agonist of the nalorphine-type. Morphine suppressed the cyclazocine abstinence syndrome. Cross-tolerance was not observed in ketocyclazocine-dependent dogs. These data are consistent with the hypothesis that there are strong and partial agonists of the mu and kappa types, and further, that physical dependence on morphine and cyclazocine is mediated through different receptors. WIN 35, 197-2 appears to be a pure strong agonist of the kappa type. Cyclazocine is a mu antagonist and mixed kappa and sigma agonist.

Topics: Animals; Behavior, Animal; Cyclazocine; Dogs; Drug Interactions; Female; Humans; Morphine; Morphine Dependence; Nalorphine; Spinal Cord; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

In rats made dependent on morphine by implantation of morphine pellets, withdrawal, as precipitated by intraventricular injection of morphine antagonists, was compared to withdrawal as precipitated by systemic antagonist application. The results, most clearly those obtained with a hydrophilic compound, diallyl-nor-morphinium-bromide, point to periventricularly located sites of action for the release of most withdrawal signs by antagonists. Jumping, reaching only low levels after i.ventr. injection of levallorphan and nalorphine, was very pronounced when the benzomorphane derivative SH 254, was used. In the case of writhing and diarrhea, the situation is more complicated. Possibly, central as well as peripheral mechanisms are involved in the expression of these signs.

Topics: Animals; Cerebral Ventricles; Humans; Injections, Intraperitoneal; Injections, Intraventricular; Levallorphan; Male; Morphinans; Morphine; Morphine Dependence; Nalorphine; Narcotic Antagonists; Rats; Receptors, Drug; Substance Withdrawal Syndrome

Single doses of serine (250 mg/kg i.p.) failed to elevate central glycine in mice (1 h after injection), or to compensate for losses caused by implantation of morphine base (70 mg/animal), and reduced the jumping response to nalorphine (100 mg/kg i.p.). In contrast, sustained treatment with 250-mg/kg doses of serine at 24-hour intervals produced increases in brain and medullar glycine (1 h after 4th injection: 46-50% in normal, 39-75% in morphine-dependent mice, and enhanced the jumping response (40% over controls).

Topics: Animals; Brain; Drug Tolerance; Glycine; Humans; Male; Mice; Morphine Dependence; Nalorphine; Serine; Strychnine; Substance Withdrawal Syndrome

Topics: Adult; Female; Heroin; Humans; Nalorphine; Substance Withdrawal Syndrome; Ventricular Fibrillation

Topics: Adenylyl Cyclases; Cell Line; Cyclic AMP; Glioma; Humans; Hybrid Cells; Models, Biological; Morphine; Nalorphine; Neuroblastoma; Neurons; Opium; Protein Conformation; Receptors, Drug; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Animals; Behavior, Animal; Drug Administration Schedule; Haplorhini; Humans; Injections, Intravenous; Macaca mulatta; Male; Morphine Dependence; Nalorphine; Reinforcement Schedule; Substance Withdrawal Syndrome; Time Factors

Topics: Aminopyrine; Analgesics; Animals; Behavior, Animal; Humans; Isonipecotic Acids; Levorphanol; Male; Methadone; Mice; Morphinans; Morphine; Morphine Dependence; Motor Activity; Nalorphine; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Animals; Behavior, Animal; Body Weight; Codeine; Dose-Response Relationship, Drug; Humans; Infusions, Parenteral; Injections, Intraperitoneal; Male; Meperidine; Methadone; Morphine; Morphine Dependence; Nalorphine; Naloxone; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vocalization, Animal

Topics: Aggression; Animals; Disease Models, Animal; Drug Synergism; Glycine; Humans; Mice; Morphine Dependence; Nalorphine; Substance P; Substance Withdrawal Syndrome

Topics: Animals; Behavior, Animal; Body Weight; Flurothyl; Humans; Male; Morphine Dependence; Nalorphine; Rats; Seizures; Substance Withdrawal Syndrome; Time Factors

Topics: Amygdala; Animals; Cerebral Cortex; Depression, Chemical; Drug Interactions; Electrophysiology; Humans; Hypothalamus; Methadone; Morphine; Morphine Dependence; Nalorphine; Naloxone; Neurons; Rats; Substance Withdrawal Syndrome; Time Factors

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Drug Synergism; Drug Tolerance; Haplorhini; Humans; Macaca; Molecular Conformation; Morphine; Nalorphine; Narcotic Antagonists; Phenols; Pyrrolidines; Rats; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Animals; Bridged-Ring Compounds; Cyclazocine; Dose-Response Relationship, Drug; Electroshock; Haplorhini; Humans; Macaca; Mice; Morphine; Morphine Dependence; Nalorphine; Naloxone; Naphthalenes; Narcotic Antagonists; Pentazocine; Postural Balance; Rats; Reaction Time; Reflex; Substance Withdrawal Syndrome; Tail

Topics: Analgesics; Animals; Cyclazocine; Female; Haplorhini; Humans; Male; Mice; Morphinans; Morphine; Morphine Dependence; Nalorphine; Naloxone; Narcotic Antagonists; Pentazocine; Stereotyped Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; Thebaine; Time Factors

Topics: Aminopyrine; Animals; Azepines; Body Weight; Codeine; Cyproheptadine; Dextropropoxyphene; Humans; Male; Meperidine; Meprobamate; Methods; Morphine Dependence; Nalorphine; Pentazocine; Pentobarbital; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Drug Tolerance; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Methadone; Nalorphine; Opium; Rehabilitation Centers; Socioenvironmental Therapy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Acetylcholine; Animals; Brain Chemistry; Dose-Response Relationship, Drug; Drug Synergism; Drug Tolerance; Hemicholinium 3; Humans; Male; Morphine; Nalorphine; Naloxone; Narcotic Antagonists; Narcotics; Rats; Scopolamine; Substance Withdrawal Syndrome; Time Factors

Topics: Administration, Oral; Animals; Body Weight; Diet; Drinking Behavior; Feeding Behavior; Humans; Injections; Male; Morphine; Morphine Dependence; Nalorphine; Rats; Substance Withdrawal Syndrome; Time Factors

Topics: Humans; Informed Consent; Injections, Intramuscular; Injections, Intravenous; Methadone; Nalorphine; Naloxone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: American Medical Association; Analgesics; Animals; Heroin Dependence; Humans; Injections, Intramuscular; Injections, Subcutaneous; Legislation, Drug; Nalorphine; Pentazocine; Substance Withdrawal Syndrome; Substance-Related Disorders; United States; World Health Organization

Topics: Conditioning, Classical; Conditioning, Operant; Conditioning, Psychological; Euphoria; Extinction, Psychological; Humans; Morphine Dependence; Nalorphine; Narcotic Antagonists; Psychotherapy; Recurrence; Reinforcement, Psychology; Self Medication; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Acetylcholine; Animals; Brain; Brain Chemistry; Hemicholinium 3; Humans; Male; Morphine Dependence; Nalorphine; Rats; Substance Withdrawal Syndrome; Time Factors

Topics: Analgesics; Animals; Benzazepines; Crystallization; Dose-Response Relationship, Drug; Female; Humans; Locomotion; Male; Mice; Morphine; Mydriatics; Nalorphine; Naloxone; Narcotic Antagonists; Oxymorphone; Pentazocine; Rabbits; Reflex; Respiration; Structure-Activity Relationship; Substance Withdrawal Syndrome; Tail; Time Factors

Topics: Animals; Female; Fenclonine; Haloperidol; Haplorhini; Humans; Hypothalamus; Injections, Intravenous; Macaca; Methadone; Methyltyrosines; Morphine; Nalorphine; Septal Nuclei; Substance Withdrawal Syndrome; Substance-Related Disorders; Thioridazine; Trifluoperazine

1. The effects of morphine, nalorphine, acetazolamide, and 10% CO(2) on brain metabolite concentrations of 24h-starved rats were studied. 2. A single dose of morphine (20mg/kg body wt.) caused an increase in brain glucose concentration (42%) and decreased concentrations of lactate (24%), pyruvate (29%), citrate (20%), alpha-oxoglutarate (16%), malate (14%) and creatine phosphate (10%) after 30min. No changes were found in adenine nucleotide concentrations. 3. The same dose of morphine increased arterial CO(2) from 5.07 to 7.60 kN/m(2) (38 to 57 Torr), decreased the pH from 7.41 to 7.31 and decreased O(2) from 14.1 to 10.8kN/m(2) (106 to 81 Torr) at 30min. 4. Rats injected with morphine three times daily (20mg/kg body wt.) for 2 weeks had no changes in brain metabolite concentrations or in blood gases 30min after their last injection. 5. Nalorphine (an antagonist of morphine) caused essentially no changes in brain metabolite concentrations in normal rats. When nalorphine (20mg/kg) was administered to rats previously treated with morphine three times daily for 2 weeks, there was an increase in brain glucose (100%), lactate (23%), pyruvate (18%) and citrate (10%) concentrations. 6. Acetazolamide (an inhibitor of carbonic anhydrase) and 10% CO(2) increased the arterial CO(2) from 4.79 to 6.78kN/m(2) (36 to 51 Torr) and from 5.32 to 10.8kN/m(2) (40 to 81 Torr) respectively. 7. Both acetazolamide and 10% CO(2) caused changes in brain metabolite concentrations similar to those for acutely administered morphine. Thus 10% CO(2) caused increased brain glucose concentration (123%) and decreased brain lactate (46%), pyruvate (34%), citrate (26%), alpha-oxoglutarate (33%), malate (45%) and creatine phosphate (7%) concentrations. No changes in adenine nucleotide concentrations were found. 8. The results indicate that the effect of morphine on brain metabolite concentrations may be accounted for by the increased [CO(2)]. 9. These findings constitute a consistent pattern of metabolic changes after acute morphine administration, morphine addiction, and withdrawal from morphine addiction.

Topics: Acetazolamide; Adenosine Diphosphate; Adenosine Triphosphate; Ammonia; Animals; Arteries; Aspartic Acid; Brain; Carbon Dioxide; Citrates; Glucose; Glutarates; Humans; Hydrogen-Ion Concentration; Lactates; Malates; Male; Morphine; Morphine Dependence; Nalorphine; Phosphocreatine; Pyruvates; Rats; Substance Withdrawal Syndrome

Topics: Animals; Arrhythmias, Cardiac; Bradycardia; Cerebral Aqueduct; Cerebral Ventricles; Fever; Humans; Injections, Spinal; Medulla Oblongata; Morphine; Morphine Dependence; Nalorphine; Pons; Rabbits; Seizures; Substance Withdrawal Syndrome

Topics: Breath Tests; Coma; False Negative Reactions; False Positive Reactions; Heroin; Humans; Medical History Taking; Methods; Nalorphine; Pharmaceutical Preparations; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Humans; Levallorphan; Male; Nalorphine; Narcotics; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Body Temperature; Brain; Carbon Isotopes; Fenclonine; Humans; Male; Mathematics; Morphine Dependence; Nalorphine; Norepinephrine; Rats; Serotonin; Substance Withdrawal Syndrome; Tritium; Tryptophan; Tyrosine

Topics: Animals; Female; Humans; Injections, Subcutaneous; Mice; Morphine; Morphine Dependence; Motor Activity; Nalorphine; Substance Withdrawal Syndrome

Topics: Animals; Atropine; Body Temperature Regulation; Cholinesterase Inhibitors; Female; Haplorhini; Humans; Macaca; Male; Morphine; Morphine Dependence; Nalorphine; Neostigmine; Parasympathomimetics; Physostigmine; Substance Withdrawal Syndrome; Time Factors; Tropanes

Injection of small quantities of morphine into the cerebral ventricular system of awake, relatively unrestrained, monkeys depressed or abolished operant food-reinforced lever pressing. After repeated injections progressively higher doses of morphine were needed to depress responding. Also, dependence could be demonstrated in these animals by precipitating specific abstinence signs with an antagonist.

Topics: Animals; Behavior, Animal; Cerebral Ventricles; Conditioning, Psychological; Drug Tolerance; Feeding Behavior; Haplorhini; Humans; Injections; Macaca; Morphine; Morphine Dependence; Nalorphine; Substance Withdrawal Syndrome; Time Factors

1. Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs. Morphine was withdrawn by washing out the reservoir with drug vehicle. The daily dose of morphine, or substitute drug received by each rat was determined by difference by estimating the drug remaining in reservoir washings.2. Withdrawal symptoms were more pronounced after 9 days than after 4 days of dosing with morphine.3. Body weight loss, maximal at 24 h, and increased defaecation during the first 7 h were the chief physiological signs of morphine withdrawal. The body weight loss was the result of hypodipsia and anorexia exacerbated by increased defaecation.4. When substituted for morphine in the reservoir, methadone and codeine completely prevented body weight loss and increased defaecation, while pethidine was effective against increased defaecation, but not against 24 h body weight loss. The opiate-antagonist analgesics pentazocine, nalorphine and cyclazocine either had no effect on withdrawal symptoms or increased their severity.5. In morphine dependent rats under continued morphine administration subcutaneous doses of the opiate-antagonists nalorphine, cyclazocine and naloxone all precipitated the withdrawal symptoms of body weight loss and increased defaecation. The weak antagonist pentazocine caused a significantly increased defaecation, but no significant change in body weight, while the opiates pethidine, codeine and methadone had no significant effect on body weight or defaecation.6. The advantages of inducing dependence by this method of dosing are discussed.

Topics: Animals; Body Weight; Codeine; Cyclazocine; Defecation; Female; Humans; Injections, Subcutaneous; Methadone; Methods; Morphine; Nalorphine; Pentazocine; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesia; Animals; Cycloheximide; Drug Synergism; Drug Tolerance; Female; Humans; Male; Mice; Morphine; Nalorphine; Picrates; Substance Withdrawal Syndrome

Topics: Animals; Codeine; Electroencephalography; Hippocampus; Humans; Male; Nalorphine; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome; Substance-Related Disorders

Every tenth lever-press of three morphine-dependent rhesus monkeys was reinforced with food. A red light, initially a neutral stimulus, was presented every third or fourth session for 5 min before and 5 min after an intravenous injection of nalorphine, a morphine antagonist that produces an immediate abstinence syndrome in morphine-dependent monkeys. After several pairings, conditioned suppression of lever pressing, heart-rate decrease, vomiting, and excessive salivation were observed during the red-light period before nalorphine injection. No conditioned electrocardiogram, respiration or temperature changes occurred. After 10 red light-nalorphine pairings, morphine administration was completely discontinued and monkeys were then tested monthly for persistence of the conditioned responses. The red light paired with saline injection continued to suppress lever pressing and to produce heart-rate decreases after 60 to 120 days of complete abstinence from morphine. Subsequently, daily presentations of the red light-saline injection complex rapidly extinguished these conditioned responses. Nevertheless, they could be rapidly reinstated by additional nalorphine injections.

Topics: Animals; Behavior, Animal; Brain; Conditioning, Psychological; Feeding Behavior; Female; Haplorhini; Heart Rate; Humans; Injections, Intravenous; Male; Morphine Dependence; Nalorphine; Respiratory Function Tests; Reward; Salivation; Substance Withdrawal Syndrome; Temperature; Vomiting

Topics: Adrenal Glands; Animals; Brain Chemistry; Dopamine; Dopamine Antagonists; Epinephrine; Fluorescence; Humans; Male; Methyltyrosines; Morphine; Nalorphine; Neurons; Norepinephrine; Substance Withdrawal Syndrome; Synaptic Transmission

Topics: Animals; Humans; Meperidine; Methadone; Methods; Mice; Morphine Dependence; Motor Activity; Nalorphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Axons; Capillaries; Histocytochemistry; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Morphine; Nalorphine; Neurons; Neurosecretion; Pituitary Gland, Posterior; Rats; Substance Withdrawal Syndrome

(1) Acute morphine treatment of rats reduced the total catecholamine content as well as the noradrenaline content of the adrenal gland. This was accompanied by increased ATPase activity and increased calcium content of the medullary cells. (2) After chronic morphine treatment, the total catecholamine content remained more or less unaltered, but the noradrenaline content was markedly increased together with the noradrenaline-containing areas, in comparison with what was observed in control animals. The ATPase activity of the medullary cells was found to be diminished along with the decreased calcium content. (3) In nalorphine-induced abstinence, a decrease in total catecholamine content together with a reduction of noradrenaline content and of noradrenaline-containing areas were observed. ATPase activity was also found to be increased with increased calcium content.

Topics: Adenosine Triphosphatases; Adrenal Glands; Analgesics, Opioid; Animals; Catecholamines; Chromaffin Cells; Drug Administration Schedule; Histocytochemistry; Male; Morphine; Nalorphine; Narcotic Antagonists; Rats; Substance Withdrawal Syndrome

Topics: Adult; Aged; Ejaculation; Heroin; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Nalorphine; Opium; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; Vomiting

Topics: Analgesia; Animals; Chromatography, Thin Layer; Codeine; Drug Tolerance; Female; Humans; Male; Mice; Morphine; Nalorphine; Substance Withdrawal Syndrome; Time Factors

Topics: Animals; Body Temperature; Dogs; Drug Tolerance; Homeostasis; Humans; Morphine; Morphine Dependence; Nalorphine; Partial Pressure; Pulse; Reflex; Respiration; Substance Withdrawal Syndrome; Time Factors

Topics: Adaptation, Physiological; Animals; Barbiturates; Dogs; Drug Tolerance; Enzyme Induction; Enzymes; Heart Rate; Humans; Hypnotics and Sedatives; Liver; Methylation; Mice; Microsomes; Morphine; Nalorphine; Narcotic Antagonists; Norepinephrine; Rats; Substance Withdrawal Syndrome; Sympathetic Nervous System; Tachyphylaxis; Tritium; Tyramine

Topics: Adrenal Medulla; Animals; Behavior, Animal; Body Temperature; Brain Chemistry; Brain Stem; Cats; Depression, Chemical; Dogs; Drug Tolerance; Epinephrine; Humans; Injections, Intraperitoneal; Monoamine Oxidase Inhibitors; Morphine; Morphine Dependence; Nalorphine; Norepinephrine; Phenobarbital; Rabbits; Rats; Substance Withdrawal Syndrome

Topics: Animals; Humans; Imipramine; Male; Mice; Morphine; Nalorphine; Postural Balance; Substance Withdrawal Syndrome

Topics: Animals; Apomorphine; Behavior, Animal; Brain Chemistry; Depression, Chemical; Disulfiram; Dopamine; Drug Synergism; Drug Tolerance; Esters; Female; Humans; Male; Methyltyrosines; Morphine; Myocardium; Nalorphine; Norepinephrine; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome

Topics: Dextromoramide; Humans; Male; Middle Aged; Nalorphine; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Cannabis; Drug and Narcotic Control; Female; Heroin; Humans; Legislation, Drug; Male; Methadone; Morphine; Nalorphine; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Three rhesus monkeys, physically dependent on morphine, were trained to press a lever for food on a fixed ratio of 10 responses. A tone, initially a neutral stimulus, was aperiodically presented every third or fourth session, 5 min before and after the intravenous injection of nalorphine, a morphine antagonist which produces an immediate withdrawal syndrome in morphine-dependent monkeys. After several sessions, conditioned suppression of food-lever response rate was observed. Conditioned bradycardia, emesis, and excessive salivation also occurred. In 40 to 45 sessions the conditioned suppression of food-lever response rate and the conditioned autonomic changes were extinguished by presenting pairings of a tone and saline injection. The monkeys were then reconditioned by presenting the tone aperiodically, every third or fourth session, 5 min before and after the intravenous injection of nalorphine. Results were similar to the initial conditioning sessions. Two rhesus monkeys not dependent on morphine were stabilized on a food schedule similar to that used for the first three monkeys. These monkeys showed no change in food-lever response rate during or after nalorphine injections.

Topics: Animals; Bradycardia; Conditioning, Operant; Extinction, Psychological; Female; Food; Haplorhini; Humans; Male; Morphine Dependence; Nalorphine; Reaction Time; Salivation; Sound; Substance Withdrawal Syndrome; Vomiting

Topics: Animals; Cerebral Ventricles; Humans; Mice; Morphine; Nalorphine; Substance Withdrawal Syndrome

Topics: Animals; Autonomic Nervous System; Behavior, Animal; Central Nervous System; Guinea Pigs; Humans; Morphine; Morphine Dependence; Nalorphine; Pharmacology; Research; Substance Withdrawal Syndrome; Toxicology; Urine

Topics: Animals; Autonomic Nervous System; Behavior, Animal; Central Nervous System; Codeine; Guinea Pigs; Humans; Morphine Dependence; Nalorphine; Pharmacology; Research; Substance Withdrawal Syndrome; Toxicology

Topics: Animals; Drug Tolerance; Ethylamines; Humans; Levallorphan; Meperidine; Mice; Morphine Dependence; Nalorphine; Narcotic Antagonists; Narcotics; Proadifen; Substance Withdrawal Syndrome

Topics: Amines; Animals; Antihypertensive Agents; Central Nervous System; Humans; Mice; Monoamine Oxidase Inhibitors; Morphine Dependence; Nalorphine; Substance Withdrawal Syndrome

Topics: Animals; Dihydroxyphenylalanine; Dogs; Drug Tolerance; Humans; Methyldopa; Methyltyrosines; Morphine; Nalorphine; Nialamide; Reserpine; Substance Withdrawal Syndrome

Topics: Body Temperature; Cordotomy; Dogs; Drug Tolerance; Heart Rate; Morphine Dependence; Nalorphine; Neurophysiology; Pharmacology; Physiology; Pulse; Pupil; Reflex; Reflex, Stretch; Research; Respiration; Spinal Cord; Substance Withdrawal Syndrome; Tendons; Toxicology

Topics: Animals; Behavior, Animal; Benzimidazoles; Codeine; Drug Tolerance; Humans; Infusions, Parenteral; Meperidine; Morphine; Morphine Dependence; Nalorphine; Rats; Substance Withdrawal Syndrome