Decrease in rat striatal acetylcholine levels by some direct- and indirect-acting dopaminergic antagonists

Abstract

Several direct- or indirect-acting dopamine receptor antagonists were found to decrease rat striatal acetylcholine levels. The maximum decrease of about 50% was produced by pimozide (0.5 mg/kg), by haloperidol (0.5 mg/kg) and by reserpine (2.5 mg/kg). The decreases in acetylcholine produced by pimozide and by haloperidol were found to be specific for the striatum and did not alter diencephalonic, mesencephalonic, cerebellar or hemispheric acetylcholine levels. Furthermore, these two drugs completely blocked the increase in striatal acetylcholine produced by the dopamine receptor agonist, apomorphine, and had no effect on striatal choline acetyltransferase and cholinesterase. These data suggest that haloperidol and pimozide act on the striatal cholinergic neurons through strong blockade of dopamine receptors. Reserpine presumably decreased striatal acetylcholine levels indirectly by depleting biogenic amines. Clozapine and 1-fenfluramine were unable to block the action of apomorphine, as was shown previously for chlorpromazine. It is thus suggested that these drugs are reversible dopamine receptor antagonists. Their weaker action in decreasing striatal acetylcholine may depend upon this property.