Differential sensitivity to amphetamine following long-term treatment with clozapine or haloperidol

When rats were pretreated for 8 consecutive days with 2.0 mg/kg haloperidol, injection of 2.5 or 5.0 mg/kg d-amphetamine 2 or 6 days later resulted in a larger increase in oral behaviors and a more prolonged period of focused sterotypy than in saline-pretreated controls. This increased sensitivity to amphetamine is consistent with the effects of a chronic haloperidol-induced increase in dopamine receptor sensitivity. In contrast, long-term treatment with either d-amphetamine or clozapine produced complex changes in the multiphasic behavioral response to amphetamine, which cannot be explained solely by a shift in the sensitivity of dopamine receptors.