Flunarizine attenuates cocaine-induced inhibition of A9 dopaminergic neurons.

The intravenous administration of cocaine (0.5-8 mg/kg) produced a dose-related inhibition of the firing rate of substantia nigra (A9) dopaminergic (DA) neurons. Pretreatment with the calcium antagonist flunarizine (5 mg/kg i.v.) prevented cocaine-induced effects but failed to antagonize the inhibition of firing induced by a low dose of apomorphine (10 micrograms/kg i.v.). This finding rules out the possibility that flunarizine antagonism of cocaine effect might depend on DA autoreceptors blockade by flunarizine. It is suggested that flunarizine, by blocking calcium influx into DA neurons, prevents DA release from dendrites, thereby counteracting the main mechanism by which cocaine inhibits dopaminergic neuronal activity.