Effects of perospirone, a novel 5-HT2 and D2 receptor antagonist, on Fos protein expression in the rat forebrain

The effects of perospirone, a novel 5-HT2 and D2 receptor antagonist, on Fos protein expression in the nucleus accumbens (NA) and dorsolateral striatum (DLSt) were compared with those of typical (i.e., haloperidol and fluphenazine) and atypical (i.e., clozapine and risperidone) antipsychotics using immunohistochemical techniques in rats. Perospirone and other antipsychotics tested at doses that exerted D2 blocking actions increased Fos-like immunoreactivity both in the NA and DLSt. However, the levels of Fos expression in the DLSt induced by perospirone and clozapine were less than those induced by haloperidol and fluphenazine. When compared the differences in numbers of Fos-positive neurons between in the NA and DLSt, perospirone, clozapine, and risperidone preferentially increased Fos expression in the NA. These findings suggest that perospirone has a preferential action on the mesolimbic (vs. nigrostriatal) dopaminergic system in inducing Fos protein in the rat brain, which may be related to its atypical antipsychotic properties.