Cholinergic-dopaminergic interaction in the striatum: the effect of 6-hydroxydopamine or pimozide treatment on the increased striatal acetylcholine levels induced by apomorphine, piribedil and d-amphetamine.

Apomorphine (1 and 2 mg/kg), piribedil (15 and 60 mg/kg) and d-amphetamine (5 and 10 mg/kg) increased rat striatal acetylcholine levels without affecting choline. Pretreatment with pimozide (0.5 mg/kg) completely antagonized the effect of apomorphine and piribedil and by itself markedly decreased striatal acetylcholine levels. d-Amphetamine signigicantly antagonized the effect of pimozide. Nine days after pretreatment with 6-hydroxydopamine plus pargyline, striatal dopamine was decreased by 78% while acetylcholine and choline levels remained unaltered. Under these conditions, the effect of d-amphetamine was completely abolished while apomorphine and piribedil were just as active as in the vehicle-treated group. The results suggest that d-amphetamine acted indirectly to increase striatal acetylcholine levels probably through the release of dopamine and/or noradrenaline, while apomorphine and piribedil acted directly at dopamine receptor sites.