Clozapine decreases neuropeptide Y-like immunoreactivity and neuropeptide Y mRNA levels in rat nucleus accumbens

The aim of this study was to evaluate the effect of acute, subchronic (14 d ays) and chronic (28 days) intraperitoneal (i.p.) administration of clozapi ne (10 or 25 mg/kg) on neuropeptide Y (NPY) system activity in the nucleus accumbens of the rat. NPY-like immunoreactivity (NPY-LI) decreased 24 h aft er subchronic clozapine while NPY mRNA after both acute and subchronic cloz apine treatment, NPY-LI levels were also reduced 8 days after cessation of chronic lower-dose treatment. Subchronic (14 days) administration of the 5- HT2A antagonist ketanserin (1 mg/kg i.p.) or the dopamine D-2/D-3 antagonis t (+/-) sulpiride (100 mg/kg i.p.) reduced NPY-LI levels, whereas the dopam ine D-1-like antagonist SCH 23390 (0.5 mg/kg i.p.), dopamine D-4 antagonist L-745,870 (1 mg/kg per os), and alpha(1)-adrenergic antagonist prazosin (0 .2 mg/kg i.p.) had no effect. There were no significant differences between the ketanserin-induced decrease in NPY-LI levels and the effects of the fo llowing two-drug combinations: ketanserin and SCH 23390, ketanserin and L-7 45,870, and ketanserin and prazosin. The study has shown that clozapine red uces NPY system activity in the rat nucleus accumbens. It seems that the ac tion of clozapine is partly mediated by blockade of 5-HT2A and D-2/D-3 dopa minergic receptors. (C) 1999 Elsevier Science B.V./ECNP. All rights reserve d.