Effects of typical and atypical antipsychotics on neuropeptide Y in rat brain tissue and microdialysates from ventral striatum

The main goal of this study was to investigate effects of typical (haloperi dol) and atypical (risperidone) antipsychotic drugs on brain regional neuro peptide Y (NPY)-like immunoreactivity (-LI) tissue concentrations and on re lease of NPY-LI in freely moving rats. An additional aim was to explore the effect of d-amphetamine on NPY-LI release following pretreatment with typi cal and atypical antipsychotics. During a 4-week period, male Wistar rats w ere fed chow to which vehicle, risperidone (1.15 mg/ 100 g food or 2.3 mg/1 00 g food), or haloperidol (1.15 mg/100 g food) were added. In one series o f experiments, the animals were sacrificed on day 30 with focused microwave irradiation, the brain regions dissected and extracted for radioimmunoassa y of NPY-LI. In another experimental series, probes were inserted into the ventral striatum. The perfusates were collected at 60-min intervals; NPY-LI was determinated by radioimmunoassay. Haloperidol significantly increased NPY-LI in hypothalamus and the occipital cortex. In contrast, haloperidol d ecreased tissue levels of NPY-LI in striatum, Moreover, haloperidol and ris peridone also significantly decreased extracellular NPY-LI concentrations i n the ventral striatum. d-amphetamine (1.5 mg/kg) significantly increased e xtracellular NPY-LI in the vehicle group. Both haloperidol and risperidone pretreatments abolished the effect of d-amphetamine. The results show that d-amphetamine as well as haloperidol and risperidone selectively and specif ically affect NPY-LI concentrations in brain tissue and microdialysates and that the effect of d-amphetamine is abolished by both typical and atypical antipsychotics. (C) 2000 Wiley-Liss, Inc.