SUBCHRONIC HALOPERIDOL ADMINISTRATION DECREASES AMINOPEPTIDASE-N ACTIVITY AND [MET(5)]ENKEPHALIN METABOLISM IN RAT STRIATUM AND CORTEX

Previously we have shown that subchronic intraperitoneal (i.p.) admini stration of haloperidol decreases the degradation of [Met(5)]enkephali n by regional brain slices (Waters et al., 1995, J. Pharmacol. Exp. Th er. 274, 783). In the present study, subchronic (7-day i.p.) administr ation of haloperidol (1 mg/kg) decreased the accumulation of aminopept idase-derived fragments Tyr and Gly-Gly-Phe-Met on cortical and striat al slices. The accumulation of Tyr-Gly-Gly, however, was not altered b y haloperidol treatment on slices from either region. Further, aminope ptidase N activity was decreased in P-2 membranes isolated from either the cortex or striatum of haloperidol treated animals. These data sug gest that the haloperidol-induced decrease in [Met(5)]enkephalin metab olism results, at least in part, from a reduction in the activity of a minopeptidase N.