Chronic treatment with neuroleptics alters neutral endopeptidase 24.11 activity in rat brain regions

Chronic administration of neuroleptics has been shown to affect the endogenous levels, mRNA, posttranslational processing, and metabolism of neuropeptides in specific regions of rat brain. Neutral endopeptidase 24.11 (NEP) is known to metabolize a variety of neuropeptide substrates, including the enkephalins and neurotensin, thus modifying or terminating the bioactivity of such peptides. In the present study, chronic treatment with haloperidol (1 mg/kg/day, 12 days) increased NEP activity in nucleus accumbens, and chronic treatment with chlorpromazine (4 mg/kg/day, 12 days) increased NEP activity in caudate putamen. Higher dosages with either compound did not significantly alter NEP activity, and none of the treatments altered NEP activity in the hypothalamus. Chronic treatment with apomorphine (5 mg/kg/day, 12 days) decreased NEP activity in both nucleus accumbens and caudate putamen. These data suggest that chronic treatment with neuroleptic drugs may lead to regionally specific alterations in the metabolism of neuropeptides.