Clozapine, but not haloperidol, increases neuropeptide Y neuronal expression in the rat hypothalamus.

Many atypical antipsychotic drugs, such as clozapine, can induce significant weight gain which can have serious implications for drug compliance and morbidity. Food intake and weight gain are regulated primarily by the hypothalamus; the arcuate nucleus (ARC) of the hypothalamus is the region initially mediating the effects of circulating hormones on food intake. Neuropeptide Y (NPY) is an important hypothalamic peptide involved in body weight regulation. Immunohistochemical staining of NPY in the ARC was carried out in male Sprague-Dawley rats treated with haloperidol (1.5 mg/kg, i.p.) or clozapine (25 mg/kg, i.p.) for 3 weeks. Clozapine, but not haloperidol, produced an increase in NPY immunoreactivity in the ARC, suggesting that effects on NPY may be involved in increases in body weight following clozapine treatment.