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The effects of acute intramuscular pretreatment with several dosages of a variety of centrally acting compounds on intravenous cocaine self-administration behavior were ascertained. Pretreatment with morphine and pentobarbital produced no change in this behavior until dosages (2.0 mg/kg and 15.0 mg/kg respectively) were administered which grossly depressed grooming, exploratory, and locomotor activity behaviors, d-amphetamine (0.5-4.0 mg/kg) and phenmetrazine (2.0-12.0 mg/kg) pretreatment produced a dose-related decrease in cocaine self-administration. Trifluoperazine in dosages of 0.01-0.1 mg/kg increased the frequency of this behavior; whereas, higher dosages (0.2, 0.4 mg/kg) grossly depressed behavior. Imipramine (10-50 mg/kg) produced a dose-related decrease in cocaine self-administration. Potential mechanisms of these drug-behavior and drug-drug interactions are discussed. [ABSTRACT FROM AUTHOR]

The effects of acute and chronic chlorpromazine treatment on psychomotor stimulant self-administration behavior in the Rhesus monkey were determined. Chlorpromazine treatment significantly increased the frequency of self-administration of cocaine, pipradrol, phenmetrazine, d-amphetamine and methylphenidate. The basis of this effect was thought to either be due to an antagonism of the reinforcing effect of these compounds or an antagonism of those actions of the psychomotor stimulants which may function in limiting their self-administration. [ABSTRACT FROM AUTHOR]

The relationships between drug dosage per injection and response rate, and drug dosage per injection and total daily drug intake were ascertained in Rhesus monkeys which self-administered cocaine, pipradrol, methylphenidate and phenmetrazine intravenously. The study demonstrated the monkeys would self-administer all of these compounds over a wide range of dosages. Furthermore, the magnitude of reinforcement, i.e., dosage per injection, and the rate of responding in self-administering these compounds were inversely related. However, total daily drug intake was independent of the dosage per injection over a wide range of dosages. The results indicate that either the subjects can compensate for large changes in unit dosage so that daily drug intake remains stable or that a direct effect of these compounds functions in limiting their self-administration. [ABSTRACT FROM AUTHOR]

The behavioral effects of chronic administration of d-amphetamine in rats at a dosage of 1 mg/kg were studied with baselines involving either food or shock reinforcement. Food reinforcement was assigned according to a fixed interval or on the basis of differential reinforcement of low rate in a multiple schedule of reinforcement. Behavioral tolerance was observed in response to chronic administration of d-amphetamine when the action of drug led to a decrease in frequency of food reinforcement regardless of the schedule of reinforcement. In the second experiment, a shock avoidance situation was employed in which each avoidance response postponed the onset of grid shock. An escape contingency was provided for occasions on which an avoidance response did not occur. The chronic administration of d-amphetamine led to a uniform increase in response rate throughout the drug regimen with the consequence of decreasing rate of shock reinforcement. An hypothesis was put forward on the basis of these results which considers the development of behavioral tolerance to amphetamine administration to be a function of the drug's action in relation to its effects on the organism's behaviour in meeting reinforcement requirements. [ABSTRACT FROM AUTHOR]

The effects of d-amphetamine (0.5-4.0 mg/kg IP) and haloperidol (0.015-1.0 mg/kg IP) alone and in combination on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of a 15-min access to the milk solution once a day, 7 days a week. d-Amphetamine was administered 15 min prior to the session and haloperidol was administered 60 min prior to the session. The interaction of these compounds was determined by repeated determination of the dose-response function for d-amphetamine in combination with different doses of haloperidol. When given alone, each drug produced a dose-dependent decrease in milk intake. In combination with haloperidol, the decrement caused by d-amphetamine was shifted to lower doses in a dose-dependent manner. Isobolographic analysis of the interaction indicates that the intermediate doses (0.03-0.06 mg/kg) of haloperidol were additive and the highest doses (0.12-0.25 mg/kg) of haloperidol were infraadditive with d-amphetamine. Dose-dependent neuropharmacological actions of these compounds may account for dose-dependent interactions.

Human volunteer subjects were trained to press a lever to avoid or escape electric shock or loss of points which could be redeemed for money at the termination of the study. The effects of pentobarbital and chlorpromazine on avoidance and escape behavior were compared. Both aversive stimuli maintained behavior which was differentially sensitive to these two drugs. Chlorpromazine caused a decrease in avoidance responding at doses which had little effect on escape responding. Pentobarbital, in contrast, suppressed avoidance responding at doses which also had a suppressant effect on escape responding.

Eight normal healthy volunteers were tested in a reaction-time task and a work-output task after 24 and 48 h of sleep deprivation with and without 96 mg of inhaled cocaine. Cardiovascular changes and verbal report of mood change and drug effect were also monitored. Sleep deprivation produced a decrement in reaction-time performance which was reversed by inhalation of cocaine. Heart rate increased after cocaine both under non sleep-deprived conditions and sleep-deprived conditions. The magnitude of the drug-induced heart rate was, however, lower when subjects were deprived of sleep for 48 h. Verbal reports of cocaine effects were similar to those reported for amphetamine, with no evidence supporting the idea of a postdrug depression immediately after the acute effects of the drug dissipated, although some rebound effects were noted 8 h after drug administration.

The effects of single oral doses of nabilone, a synthetic cannabinoid, were studied in four anxious volunteer subjects. Each subject had two exposures to placebo and three dose levels of nabilone at 1 week intervals in a single blind balanced Latin square design after the nabilone dose range was determined by each subject's response to a test dose. The Profile of Mood States (POMS), a self-rating adjective checklist, was used as the quantitative measure of subjective effects. The subjects performed a continuous avoidance procedure. High doses (4 or 5 mg) of nabilone produced orthostatic hypotension. Small dose-related increases in heart rate also occurred. Despite the occurrence of highly significant levels of subjective sedation, there were no significant effects of nabilone on behavior maintained by the continuous avoidance procedure. Two of these subjects experienced an anti-anxiety effect from low (1 or 2 mg) nabilone doses, but there was no statistically significant effect on the mean POMS anxiety factor for the group as a whole. In a follow-up experiment, four other anxious subjects received comparatively lower doses of nabilone. In these subjects there were no important effects on blood pressure or heart rate, and also no anti-anxiety effects.