ABSTRACT
Two experiments were performed to verify the validity of a biotelemetry system for 24 hour recording of heart rate (HR) of rats in behavioral toxicology. As test substance the hallucinogenic drug cyclazocine was used at various dose levels (0.1, 0.75, 1.5 and 3.0 mg/kg SC). In a first experiment, female rats were tested in their home cage. It was found that HR was altered by cyclazocine during the four hours following drug injection. This alteration was biphasic: immediately after injection, when control HR was high, cyclazocine lowered HR. In contrast, one hour after the injection, when control HR was low, cyclazocine increased HR. The duration of this increase of HR was dose-dependent, while the magnitude was not. In a second experiment male rats were tested in a residential maze: simultaneously to the rat's HR, locomotor activity was recorded. The results of the first experiment were confirmed and extended to males as well as to a different environmental situation. The additional behavioral data showed a different aspect of cyclazocine action: 0.75 mg/kg initially decreased and later increased activity while 3.0 mg/kg first did not alter activity and later increased it, leading to a dissociation between HR and activity. The findings demonstrate that recording of HR adds a new dimension to the data obtained in conventional behavioral tests. The results are discussed with regard to behavioral and neurochemical effects of the drug.
Subject(s)
Cyclazocine/toxicity , Heart Rate/drug effects , Motor Activity/drug effects , Telemetry/instrumentation , Animals , Arousal/drug effects , Dose-Response Relationship, Drug , Female , Male , Rats , Rats, Inbred Strains , Social EnvironmentABSTRACT
The induction side effects of cyclazocine and naltrexone were compared in double-blind placebo-controlled studies involving 40 patients (20 for each drug). These studies were carried out with a twice-a-day dosage regimen. Naltrexone produced fewer side effects than cyclazocine. Naltrexone side effects fell to levels indistinguishable from those of placebo in the "induction after placebo" phase. In contrast, cyclazocine "induction after placebo" produced an even higher level of side effects than found in its induction. In no case was naltrexone discontinued because of side effects. On the other hand, three of 20 cyclazocine-treated patients discontinued the drug because of distressing side effects. No toxicity was noted with either agent. The controlled data reported supports the clinical impression that naltrexone produces fewer induction side effects than cyclazocine.
Subject(s)
Cyclazocine/adverse effects , Heroin Dependence/drug therapy , Naloxone/analogs & derivatives , Naltrexone/adverse effects , Administration, Oral , Adult , Cyclazocine/administration & dosage , Cyclazocine/toxicity , Double-Blind Method , Humans , Male , Naltrexone/administration & dosage , Naltrexone/toxicity , Placebos , Self-AssessmentABSTRACT
This study examines the lethality of combinations of central nervous system stimulants, narcotics and narcotic antagonists in rodents housed individually. The lethality of mice and rats from d-amphetamine was potentiated by methadone, cyclazocine and morphine, in that order of potency. Naloxone did not enhance lethality from d-amphetamine in mice, whereas it did antagonize lethality from morphine-d-amphetamine interactions. Naloxone did slightly enhance lethality from d-amphetamine in rats, but at a higher dose than those found to antagonize the lethality from morphine-d-amphetamine combinations. Methadone also enhanced the lethality from cocaine. These results have important implications for drug abusers and for patients being treated for narcotic addiction with either a methadone maintenance program or a cyclazocine administration program.
