Chronic treatment with chlorpromazine, thioridazine or haloperidol increases striatal enkephalins and their release from rat brain.

The aim of this paper is to study the effect of 1, 2 or 3 months' administration of chlorpromazine (CPZ), thioridazine (TDZ) (2 or 6 mg/kg) or haloperidol (HAL) (0.25 or 1 mg/kg) IP on the level of leu- and met-enkephalin (ENK) in striatum. A dose- and time-dependent increase of striatal ENK level was observed after chronic administration of the neuroleptics (NL), but 8 days after withdrawal of chronically administered NL striatal ENK was decreased. Apomorphine pretreatment significantly attenuated the elevation in ENK produced by chronic injections of NL. In perfusion fluid obtained from the lateral ventricle of animals treated 1 month with HAL a dose-dependent increase of ENK levels was observed, which was augmented by potassium ions. It is concluded that: 1) Chronic administration of neuroleptic drugs that block dopamine receptors increases the level and the release of striatal enkephalins; 2) The results support the hypothesis that activation of dopaminergic neurons tonically inhibits the synthesis of enkephalins in the striatum.