EFFECT OF A NOVEL ANTIPSYCHOTIC PEROSPIRONE (SM-9018) ON FOS PROTEIN EXPRESSION IN THE RAT FOREBRAIN

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.2; p. 267
• Main Authors: Ishibashi, Tadashi, Ohno, Yukihiro, Tokuda, Kumiko, Tojima, Rie, Nakamura, Mitsutaka
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)37308-1

Immunohistochemical studies were performed to compare the effect of perospirone, a novel antipsychotic candidate, on Fos protein expression in the rat forebrain with those of typical (haloperidol and fluphenazine) and atypical (clozapine and risperidone) antipsychotics. Fos expression was evaluated by immunostaining the Fos protein with the anti-Fos polyclonal antibody, and quantified by counting the number of Fos-positive neurons within the grid (500 × 500 μm) in various regions of the brain. Perospirone (10 mg/kg, p.o.) markedly increased Fos expression in the nucleus accumbens, moderately in the prefrontal cortex, the lateral septum, the claustrum and the dorsomedial striatum, but sparsely in the dorsolateral striatum. Other antipsychotics also increased the Fos-positive neurons in these brain regions except fluphenazine which did not increase the Fos expression in the prefrontal cortex and the lateral septum. In addition, perospirone- and clozapine-induced Fos expression in the dorsolateral striatum were much smaller that those induced by haloperidol and fluphenazine. When the numbers of Fos-positive neurons were compared between in the nucleus accumbens and in the dorsolateral striatum, perospirone, clozapine and risperidone preferentially increased the Fos expression in the former structure, but haloperidol and fluphenazine in the latter structure. These findings suggest that perospirone, like the atypical antipsychotic clozapine, has a preferential action on the mesolimbic (vs. nigrostriatal) dopaminergic system in inducing the Fos protein in the rats brain.