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) intraperitoneal (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 lowest after haloperidol. NPY-LI levels increased 8 days after withdrawal of chronic drugs treatment. Acute administration of haloperidol reduced NPY mRNA, while Subchronic treatment did not change it. Subchronic i.p. administration of the dopamine D1-like antagonist SCH 23390 (1 mg/kg) reduced NPY-LI levels but the alpha1-adrenergic antagonist prazosin (0.2 mg/kg) had no effect. The effect of sulpiride coadministered with SCH 23390 was greater than that of SCH 23390 alone, while prazosin coadministered with sulpiride insignificantly reduced the effect of sulpiride. The dopamine D2/D3 agonist quinpirole given as a single injection (3 mg/kg) did not alter NPY-LI content by itself but antagonized the chlorpromazine-induced decrease and attenuated the haloperidol-induced decrease. Our findings indicate that the accumbens NPY system is markedly affected by the antipsychotics studied, and suggest that their effects may be in part mediated by blockade of D2-like (D2, D3) and D1 dopaminergic receptors.