Effects of preceding sensibilization by reserpine and haloperidol on toxicity of dopaminergic agonists

The effect of dopaminergic supersensitivity induced by repeated administration of neuroleptics on the toxicity of amphetamine in mice has been examined. As well as haloperidol, reserpine pretreatment increased the toxicity of amphetamine. Combined pretreatment did not cause a further increase of mortality following amphetamine. Dose response curves were not parallel, which might indicate different causes of death in naive and sensitized mice. Pretreatment with haloperidol did not change the toxicity of reserpine. The potentiating effects of neuroleptics on amphetamine toxicity may be connected with their ability to induce supersensitivity to dopaminergic agonists.