Effects of acute or long-term treatment with chlorpromazine, haloperidol or sulpiride on neuropeptide Y-like immunoreactivity concentrations in the nucleus accumbens of rat

The effects of acute, subchronic (14 days) or chronic (28 days) intraperito neal (i.p.) administration of chlorpromazine (2 or 10 mg/kg), haloperidol ( 0.5 or 2 mg/kg) or sulpiride (50 or 100 mg/kg) on the neuropeptide Y (NPY) system in the rat nucleus accumbens were studied, NPY-like immunoreactivity (NPY-LI) decreased in a dose- and time-dependent manner, and was the lowes t after haloperidol. NPY-LI levels increased 8 days after withdrawal of chr onic drugs treatment. Acute administration of haloperidol reduced NPY mRNA, while subchronic treatment did not change it. Subchronic i.p. administrati on of the dopamine D-1-like antagonist SCH 23390 (1 mg/kg) reduced NPY-LI l evels but the alpha(1)-adrenergic antagonist prazosin (0.2 mg/kg) had no ef fect. The effect of sulpiride coadministered with SCH 23390 was greater tha n that of SCH 23390 alone, while prazosin coadministered with sulpiride ins ignificantly reduced the effect of sulpiride. The dopamine D-2/D-3 agonist quinpirole given as a single injection (3 mg/kg) did not alter NPY-LI conte nt by itself but antagonized the chlorpromazine-induced decrease and attenu ated the haloperidol-induced decrease. Our findings indicate that the accum bens NPY system is markedly affected by the antipsychotics studied, and sug gest that their effects may be in part mediated by blockade of D-2-like (D- 2, D-3) and D-1 dopaminergic receptors. (C) 1999 Elsevier Science B.V./ECNP . All rights reserved.