Subchronic haloperidol administration decreases aminopeptidase N activity and [Met⁵]enkephalin metabolism in rat striatum and cortex

Previously we have shown that subchronic intraperitoneal (i.p.) administration of haloperidol decreases the degradation of [Met⁵]enkephalin by regional brain slices (Waters et al., 1995, J. Pharmacol. Exp. Ther. 274, 783). In the present study, subchronic (7-day i.p.) administration of haloperidol (1 mg/kg) decreased the accumulation of aminopeptidase-derived fragments Tyr and Gly-Gly-Phe-Met on cortical and striatal slices. The accumulation of Tyr-Gly-Gly, however, was not altered by haloperidol treatment on slices from either region. Further, aminopeptidase N activity was decreased in P₂ membranes isolated from either the cortex or striatum of haloperidol-treated animals. These data suggest that the haloperidol-induced decrease in [Met⁵]enkephalin metabolism results, at least in part, from a reduction in the activity of aminopeptidase N.