D1 and D2 receptor antagonists differently affect cocaine-induced locomotor hyperactivity in the mouse.

Pretreatment with small, per se ineffective doses of the selective D1 antagonist SCH 23390 inhibited hyperactivity induced by cocaine. On the other hand, the classic neuroleptic haloperidol and the selective D2 antagonist metoclopramide prevented the stimulatory effects of cocaine on locomotion only at hypokinetic doses, while the atypical neuroleptic (-)-sulpiride, a selective D2 antagonist, did not produce significant effects when administered at the hypokinetic dose of 12 mg/kg. Finally, at low doses (-)-sulpiride dose-dependently potentiated the locomotor-stimulating effects of cocaine, an effect that is not shared either with haloperidol or with metoclopramide. These results are discussed in terms of different roles of DA receptor subtypes in the modulation of the stimulant effects of cocaine on locomotion.