Influence of typical and atypical antipsychotics on neuropeptide Y-like immunoreactivity and NPY mRNA expression in rat striatum.

Striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels were investigated in naive rats after acute, subchronic (14 days) or chronic (28 days) intraperitoneal (i.p.) treatment with chlorpromazine (2 or 10mg/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 were found 24 h after acute chlorpromazine or haloperidol administration (a decrease) and after withdrawal of chlorpromazine, haloperidol or sulpiride (an increase). The effect of clozapine on NPY-LI differed from those of the other antipsychotics: both single doses had no effect, the higher chronic dose increased NPY-LI levels, and its withdrawal resulted in their decrease. No significant alterations were detected in the hybridization signal of NPY mRNA in response to acute or subchronic administration of haloperidol or clozapine. Our results suggest that the effects of antipsychotics are in part mediated by blockade of dopamine D2-like (D2/D3) or serotonin 5HT2A receptors but not dopamine D1, D4 or alpha1-adrenergic receptors. The antipsychotic-induced changes in NPY system activity has been discussed in connection with adaptive alterations in the dopamine system.