INFLUENCE OF TYPICAL AND ATYPICAL ANTIPSYCHOTICS ON NEUROPEPTIDE Y-LIKE IMMUNOREACTIVITY AND NPY MESSENGER-RNA EXPRESSION IN RAT STRIATUM

Striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels were inv estigated in naive rats after acute, subchronic (14 days) or chronic ( 28 days) intraperitoneal (i.p.) treatment with chlorpromazine (2 or 10 mg/kg), haloperidol (0.5 or 2 mg/kg), (+/-)sulpiride (50 or 100 mg/kg ) or clozapine (10 or 25 mg/kg), and in chronically treated rats after 8-day drug withdrawal. The most pronounced changes in NPY-LI levels w ere found 24 h after acute chlorpromazine or haloperidol administratio n (a decrease) and after withdrawal of chlorpromazine, haloperidol or sulpiride tan increase). The effect of clozapine on NPY-LI differed fr om those of the other antipsychotics: both single doses had no effect, the higher chronic dose increased NPY-LI levels, and its withdrawal r esulted in their decrease. No significant alterations were detected in the hybridization signal of NPY mRNA in response to acute or subchron ic administration of haloperidol or clozapine. Our results suggest tha t the effects of antipsychotics are in part mediated by blockade of do pamine D-2-like (D-2/D-3) or serotonin 5HT(2A) receptors but not dopam ine D-1, D-4 or alpha(1)-adrenergic receptors. The antipsychotic-induc ed changes in NPY system activity has been discussed in connection wit h adaptive alterations in the dopamine system.