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

ABSTRACT

The main goal of this study was to investigate effects of typical (haloperidol) and atypical (risperidone) antipsychotic drugs on brain regional neuropeptide Y (NPY)-like immunoreactivity (-LI) tissue concentrations and on release 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 typical and atypical antipsychotics. During a 4-week period, male Wistar rats were fed chow to which vehicle, risperidone (1.15 mg/100 g food or 2.3 mg/100 g food), or haloperidol (1.15 mg/100 g food) were added. In one series of experiments, the animals were sacrificed on day 30 with focused microwave irradiation, the brain regions dissected and extracted for radioimmunoassay 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 determined by radioimmunoassay. Haloperidol significantly increased NPY-LI in hypothalamus and the occipital cortex. In contrast, haloperidol decreased tissue levels of NPY-LI in striatum. Moreover, haloperidol and risperidone also significantly decreased extracellular NPY-LI concentrations in the ventral striatum. d-amphetamine (1.5 mg/kg) significantly increased extracellular 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 specifically affect NPY-LI concentrations in brain tissue and microdialysates and that the effect of d-amphetamine is abolished by both typical and atypical antipsychotics.