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Chronic prior treatment with amphetamine greatly attenuates the conditioned aversion to saccharin that may be produced by amphetamine. Two experiments were designed to determine some of the limiting conditions of this phenomenon. In Experiment 1, chronic treatment with 7.5 mg/kg of amphetamine was administered for 0, 1, 5, or 20 days prior to pairing saccharin with an injection of 1.0 mg/kg of d-amphetamine sulphate. The results indicated that between 5 and 20 days of treatment were necessary for the treatment to be effective in attenuating conditioned aversion. In Experiment 2, rats were withdrawn from treatment with 20 mg/kg of amphetamine for 1, 7, or 14 days prior to conditioning trials with 1.0 mg/kg of amphetamine. The prior treatment lost its effectiveness in attenuating conditioned aversion between 7 and 14 days after withdrawal. Although alternative explanations are possible, the time intervals required for acquisition and loss of the effectiveness of prior treatment are consistent with the hypothesis that tolerance is the mechanism underlying the observed effects. [ABSTRACT FROM AUTHOR]

Although psychosocial variables affect the consequences of marihuana ingestion, little is known of the role of such variables as determinants of the self-administration of the drug. To pursue this question, three variables were manipulated in a factorial design. Marihuana use history was manipulated by selecting subjects at extremes of use frequency. To determine the possible contribution of learned smoking habits to consumption, subjects smoked either large or small cigarettes. Finally, cigarettes varying in concentration of delta-9 tetrahydrocannabinol (0.36%, 0.73% or 1.45%) were used. Subjects were simply asked to smoke until they had attained a 'nice high'. Although there was some evidence of titration according to potency, subjects self-administrated more total tetrahydrocannabinol the more potent the material in attaining the same subjective endpoint of intoxication. More material was ingested in the form of large than small cigarettes. The latter variable accounted for nearly as much variance as did drug potency itself. This result illustrated the importance of an essentially cognitive variable as a determinant of drug intake. Finally, there was no difference in the amount required by frequent and infrequent users to attain the intoxication criterion. The latter result was in opposition to the assertion by Nahas (1973) that frequent exposure to cannabis will ultimately result in an increase in the amount required to produce the reinforcing effects of marihuana. It was emphasized that assertions about the contribution of various factors to drug-taking behavior should be withheld in the absence of data from experiments in which actual self-administration is the dependent variable. [ABSTRACT FROM AUTHOR]

Previous research has suggested that psychosocial rather than strictly pharmacological factors may play a dominant role in the subjective response to 'socially relevant' (i.e., low) doses of marihuana. The insensitivity of experienced marihuana users to pharmacological factors was studied in an ad lib self-administration situation. Subjects tested repeatedly with varying drug potencies were asked to smoke a sufficient amount to achieve a predefined subjective state of intoxication. Several indices of amount consumed suggested that effective titration of intake did not occur. Rather, subjects consumed more total THC the greater the potency of the material. Doses which produced a subjectively 'optimal high' had significant behavioral and physiological effects. The results are consistent with the hypothesis that psychosocial variables may be more significant than pharmacological variables in determining the recreational intake of marihuana. [ABSTRACT FROM AUTHOR]

Some investigators have used evidence that a drug may induce conditioned taste aversion to dismiss other behavioral effects of the drug as due to general toxicity rather than specific pharmacological action. To test the validity of this position, behaviorally relevant doses of alcohol, chlordiazepoxide, and morphine were studied in an aversive taste conditioning paradigm. Drug injections were paired with exposure to saccharin solution on repeated trials. Each drug produced saccharin aversion at one or more doses. Since comparable doses are known to facilitate rather than impair behavior in some situations, the taste aversion test is insufficient to establish the general behavioral toxicity of particular drug doses. [ABSTRACT FROM AUTHOR]

A constraint upon intravenous drug self-administration techniques is that they are suitable only for assessing positively reinforcing consequences of drug action; they do not permit a distinction among several possible explanations for reduced or zero rates of self-administration by animals. The possibility that there is a significant punishing component to drug administration was investigated in an aversive taste conditioning paradigm. Mescaline, which is refused by monkeys, and d-amphetamine, which is self-administered by both rats and monkeys, were compared. Five min after drinking saccharin solution for the first time, groups of rats were injected intraperitoneally with saline or different doses of each drug. Conditioned taste aversion was clearly demonstrated with both drugs; on a second exposure to saccharin solution, fluid consumption was greatly depressed compared to control values. This was true even with a dose of d-amphetamine (2 mg/kg) known to be self-administered by rats. The results suggest that intravenous drug self-administration may involve a punishing component which is detectable only in an appropriate behavioral test. It was also noted that aversive taste conditioning was demonstrable at doses frequently used in behavioral pharmacological investigations. [ABSTRACT FROM AUTHOR]

Rats were given the opportunity to drink morphine solution following stabilization at three levels of 'passive premedication'. Compared to saline treated controls, premedicated rats consumed more morphine solution, but medication level did not significantly affect morphine intake. Premedicated rats adjusted to a reduction in morphine solution concentration by increasing fluid intake substantially, but nonpremedicated rats did not. When morphine was offered in a vehicle of isotonic saline oral consumption rose sharply in premedicated rats but not in their nonpremedicated counterparts. 'Drinker' and 'nondrinker' rats were identified on the basis of initial response to oral morphine. Premedication eliminated resistance to morphine drinking, but even at the expense of severe fluid deprivation, nonpremedicated nondrinkers refused morphine throughout the entire experiment. [ABSTRACT FROM AUTHOR]