nalorphine and Body-Weight

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

The analgesic activity of O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride was investigated in Swiss--Webster mice using an electroshock technique in which the pain threshold was the minimum voltage producing tonic extension of the hindlimbs in response to an electroshock delivered to the feet. The analgesic potency of O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride was equal to, or greater than, that of morphine. Neither nalorphine nor withdrawal produced visible behavioral effects in rats treated with O-(4-methoxylphenylcarbamoyl)-3-diethylaminopropiophenone oxime hydrochloride for 21 days, suggesting that the physical dependency liability of the compound may be less than that of morphine.

Topics: Analgesics; Animals; Behavior, Animal; Body Weight; Humans; Male; Mice; Morphine; Nalorphine; Oximes; Propiophenones; Rats; Reaction Time; Sensory Thresholds; Substance-Related Disorders

Groups of naive rats were offered morphine sulfate for self-admininstration in doses of 0.0032-10 mg/kg for 6 days. On day 7 saline was substituted for morphine. Loss of weight was taken as physiological evidence of dependence. Rats that did not lose weight formed a single population whose mean injection rate did not differ from control rats receiving only saline injections. Injection rates for rats losing weight were log-normally distributed, and the mean of the logarithms of the injection rates was linearly related to the logarithm of the dose. Mean daily injection rates averaged 12 for controls, 23 at 10 mg/kg, and 411 at 0.01 mg/kg. A transient increase in morphine intake after an injection of nalorphine was taken as behavioral evidence of dependence. Nalorphine increased morphine intake when rats were self-injecting 0.32 and 1.0 mg/kg of morphine, but not 0.032 or 0.1 mg/kg. The reinforcing property of morphine may occur without behavioral evidence of dependence.

Topics: Animals; Body Weight; Conditioning, Operant; Dose-Response Relationship, Drug; Extinction, Psychological; Female; Humans; Morphine; Morphine Dependence; Nalorphine; Rats; Self Administration; Time Factors

A standardized self-administration procedure in rats was used to determine the intravenous self-administration liability of graded doses of various drugs. Self-administration was reliably established with the tested addictive drugs (morphine, heroin, fentanyl and d-amphetamine), but not with the nonaddictive drugs (chlorpromazine and nalorphine). However, 1 out of 14 animals on nalorphine clearly demonstrated self-administering behavior. Self-administration was observed with delta1-tetrahydrocannabinol, but the percentage of animals (40% on the highest dose) that initiated this behavior and the amount of drug intake were low in comparison with amphetamine and narcotics. Concerning the narcotic drugs, approximate ED50 values for self-administration under the described conditions were calculated (morphine: 0.65; heroin: 0.05; fentanyl: 0.0025 mg/kg/injection). Total daily drug intake was related to the unit dose delivered per injection in that a higher drug dosage led to more drug intake. In experiments with heroin, this relationship was not caused by prior forced injections. The approximate ED50 value for amphetamine appeared to be 0.145 mg/kg/injection. Narcotic drug administration resulted in a disturbance of the patterns of food and water intake. Shortly after drug administration food intake was stimulated, followed by an increased consumption of water. The patterns of food and water intake remained disturbed in animals showing self-injecting behavior. With amphetamine both the quantity of food and the frequency of eating were reduced. These effects were observed only temporarily in animals tested without prior forced injections. The present results indicate that measuring the reinforcing efficacy of drugs under strictly defined experimental conditions provides quantitative criteria for intravenous self-administration of drugs in rats.

Topics: Animals; Behavior, Animal; Body Weight; Chlorpromazine; Dextroamphetamine; Drinking; Dronabinol; Eating; Female; Injections, Intravenous; Nalorphine; Narcotics; Pharmaceutical Preparations; Rats; Self Administration

Neonatal mice were treated with d,1-methadone, 1-alpha-acetylmethadol (LAAM) or the narcotic antagonists, naloxone, nalorphine or levallorphan. Litter mates were injected with normal saline solution and handled in the same way. Treatment began on the second postpartum day and continued daily or on alternate days for up to 6 weeks. Injection of methadone in dosages of 2 mg/kg to mg/kg inhibited weight gain in a log dose-related fashion. LAAM, 1 mg/kg or 2 mg/kg also retarded weight gain. Mice gained weight normally when naloxone, 10 mg/kg was injected with methadone, 2 mg/kg. Furthermore the daily injection of d-methadone, 4 mg/kg, did not inhibit weight gain nor did any of the narcotic antagonists. There findings indicate that growth inhibition induced by methadone is a stereospecific, opioid effect.

Topics: Animals; Animals, Newborn; Appetite Depressants; Body Weight; Depression, Chemical; Drug Tolerance; Female; Growth; Levallorphan; Methadone; Methadyl Acetate; Mice; Nalorphine; Naloxone; Reaction Time; Stereoisomerism; Time Factors

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

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

Topics: Analgesics; Animals; Body Weight; Cyclazocine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Mice; Morphine; Motor Activity; Nalorphine; Naloxone; Narcotic Antagonists; Placebos; Reflex; Tail; 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: Analgesics; Animals; Antitussive Agents; Body Weight; Cardiovascular System; Constriction; Digestive System; Drug Synergism; Drug Tolerance; Humans; Hypotension; Male; Meperidine; Methods; Mice; Morphine; Nalorphine; Piperidines; Pupil; Rats; Respiration; Substance-Related Disorders; Thiopental

Topics: Analgesics; Anesthetics, Local; Animals; Anti-Inflammatory Agents; Antitussive Agents; Blood Pressure; Body Weight; Cats; Central Nervous System; Cerebral Cortex; Codeine; Constipation; Dogs; Electrocardiography; Electroencephalography; Female; Guinea Pigs; Heart; Heart Rate; Histamine H1 Antagonists; In Vitro Techniques; Male; Mice; Morphinans; Nalorphine; Pentobarbital; Pentylenetetrazole; Rabbits; Rats; Respiration; Stimulation, Chemical; Thiopental; Time Factors

Topics: Acridines; Animals; Body Weight; Female; Fetus; Growth; Morphinans; Morphine; Nalorphine; Oxides; Pregnancy; Rats; Spleen; Stomach; Thiazoles

Topics: Animals; Body Weight; Chickens; Comb and Wattles; Luteinizing Hormone; Male; Morphine; Nalorphine; Pituitary Gland; Testis

Topics: Animals; Animals, Newborn; Apnea; Body Weight; Dyspnea; Hypoxia; Levallorphan; Meperidine; Morphine; Nalorphine; Rabbits; Respiratory Function Tests

Topics: Animals; Body Weight; Feces; Female; Genetics; Male; Morphine; Nalorphine; Rabbits