Behavioral toxicity of amphetamine is differentially affected by hot and cold water immersion stress.

The interaction of two qualitatively different but behaviorally equivalent stressors with the behavioral toxicity induced by d-amphetamine (AMPH) was examined in rats. Stress, administered by immersing the rats in either hot or cold water, suppressed fixed ratio 15 (FR15) operant responding 50% and disrupted thermoregulation. AMPH (1, 2 and 3 mg/kg) administered immediately prior to stress, once every 7 days, in ascending order, did not modify stress-induced changes in colonic temperature (Tc) immediately after water immersion but induced a decrease in Tc in all groups 45 min later. The behavioral suppressant effect of AMPH observed in the Non-Stressed group was attenuated at all doses in rats exposed to cold water. Although both stressed groups had equivalent baseline rates, only the Cold-Stressed group's response rate was relatively unaffected by AMPH, compared to non-drug response rates, as would be predicted by the rate-dependency hypothesis. The hot stress appears to have activated processes antagonistic to those involved in the rate-dependent effect. The results indicate that AMPH interacts with hot and cold stressors differently when the intensity of the stressors are otherwise equivalent in their ability to alter the behavior which is used as the dependent variable to assess toxicity.