Flunarizine potentiates cocaine-induced doparaine release and motor stimulation in rats

Pretreatment with fiunarizine (20 mg/kg), a diphenylalkylamine calcium channel antagonist, markedly potentiated cocaine (10 mg/kg) -induced dopamine (DA) output from the ventral striatum, as measured by microdialysis in freely moving rats. Moreover, fiunarizine enhanced cocaine-induced motor stimulation. Pretreatment with the D2 receptor antagonist (-)-sulpiride (25 mg/kg) potentiated cocaine-induced DA output but, unlike fiunarizine, inhibited cocaine-induced motor stimulation. When added to striatal membrane preparations, flunanzine displaced [3H]spiperone binding with a Ki of about 100 nM. Since recent evidence indicates that the effects of cocaine are calcium-dependent and are prevented by dihydropyridine calcium antagonists, these findings suggest that the paradoxical potentiating effect of fiunarizine is probably due to an interaction with the DA system and is not due to its calcium antagonist property. © 1990.