Conditioned aversion by amphetamine: rates of acquisition and loss of the attenuating effects of prior exposure.

Chronic prior treatment with amphetamine greatly attenuates the conditined 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 indicate 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 In Experiment 2, rats were withdrawn from treatment with 20 mg/kg of amphetamine for 1, 7, or 14 days prior to conditioning trials with 1.0 mg/kg of amphetamine.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 it 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.