Choline High‐Affinity Uptake and Metabolism and Choline Acetyltransferase Activity in the Striatum of Rats Chronically Treated with Neuroleptics

Abstract

: High‐affinity uptake of choline and choline acetyltransferase activity (ChAT) were measured in the striatum of rats treated for 45–60 days with haloperidol (1 mg/kg per os) and pimozide (1 mg/kg per os) daily and with fluspirilene (1 mg/kg i.m.) twice a week. Haloperidol and fluspirilene caused a 29%, and pimozide a 38%, increase in high‐affinity uptake of choline. They also caused a significant decrease in ChAT activity: haloperidol, 20%; pimozide, 27%; and fluspirilene, 42%. In rats treated with fluspirilene for 65–80 days the metabolism of [³H]choline taken up by striatal synaptosomes was investigated. A 33% increase in total radioactivity, a significant increase in labelled acetylcholine (ACh), a relative decrease in labelled choline, and no change in labelled phosphorylcholine and betaine were found. It is concluded that the increase in high‐affinity choline uptake caused by chronic administration of neuroleptic drugs is associated with a parallel increase in choline utilization for ACh formation. On the other hand, the decrease in ChAT activity does not appear to influence ACh formation.