Effects of chronic treatment of olanzapine and haloperidol on peptide YY binding densities in the rat brain

This study examined regional changes of peptide YY (PYY) binding densities in the rat brain after chronic administration of olanzapine (1.2 mg/kg/day) and haloperidol (2.0 mg/kg/day) for 36 days. PYY binding densities and distributions were detected by [125I] binding autoradiography after rats were sacrificed either 2 h or 48 h after the last drug administration to examine both immediate and delayed effects following the drug withdrawal. Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52%, p < 0.05), dorsal part of medial geniculate nucleus (56%, p < 0.05), superficial gray layer of the superior colliculus (53%, p < 0.05), parabrachial pigmented nucleus (54%, p < 0.05) and periaqueductal gray (50%, p < 0.05) compared to controls, while rebound increases of PYY binding densities were observed in most of examined regions 48 h later with only medial geniculate nucleus dorsal showing significant increase compared to controls (118%, p < 0.01). In contrast, no change in PYY binding densities was found in the haloperidol-treated groups 2 h after drug administration, while only a significant rebound increase was observed in the dorsal part of medial geniculate nucleus (94%, p < 0.01) 48 h after the haloperidol withdrawal. Alterations in PYY binding densities in brain regions such as the dorsal part of medial geniculate nucleus, superficial gray layer of superior colliculus, periaqueductal gray and parabrachial pigmented nucleus may represent the specific regions that mediate the clinical effects of antipsychotics via neuropeptide Y system. Our study also implicates NPY receptors as a novel therapeutic target in the treatment of psychotic disorders.