CHRONIC TREATMENT WITH NEUROLEPTICS ALTERS NEUTRAL ENDOPEPTIDASE 24.11 ACTIVITY IN RAT-BRAIN REGIONS

Chronic administration of neuroleptics has been shown to affect the en dogenous 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 substrat es, including the enkephalins and neurotensin, thus modifying or termi nating the bioactivity of such peptides. In the present study, chronic treatment with haloperidol (1 mg/kg/day, 12 days) increased NEP activ ity 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 N EP activity in both nucleus accumbens and caudate putamen. These data suggest that chronic treatment with neuroleptic drugs may lead to regi onally specific alterations in the metabolism of neuropeptides.