The effect of haloperidol on cocaine self-administration is augmented with repeated administrations

Administration of haloperidol (0.075 mg/kg) prior to a 4-h self-administration session increases cocaine intake by male rats. Animals pretreated daily with haloperidol showed a significant augmentation of this response, with cocaine intake climbing from 37% above baseline to 65% above baseline in 7 days. Control rats given two treatments of haloperidol 7 days apart showed no augmentation of the response. This increased drug effect is unusual, since most behavioral actions of haloperidol in laboratory animals show tolerance. In humans, the antipsychotic activity of neuroleptic drugs requires many days to develop. Cocaine self-administration behavior might therefore provide a model for antipsychotic drug action.