Abstract
Atypical antipsychotic drugs (APDs) typified by clozapine differ from the typical agents (e.g., haloperidol) by displaying superior efficacy in the treatment of negative symptoms and reduced liability of motor side effects (EPS). The clinical efficacy of APDs is thought to involve participation of the prefrontal cortex (for negative symptoms) and nucleus accumbens (for positive symptoms) whereas the caudate-putamen may be the site underlying EPS. In agreement, our previous studies have demonstrated: a) induction of the neurotensin and c-fos gene in rat caudate by only typical APDs; but b) induction of the neurotensin gene in the nucleus accumbens-shell by all clinically efficaceous APDs. In the present study, we investigated alterations in c-fos mRNA expression in rat prefrontal cortex following haloperidol, clozapine, and a new putative atypical APD, remoxipride. Acute administration of clozapine (20 mg/kg, i.p.) markedly increased c-fos mRNA expression in deep layers of the infralimbic and ventral prelimbic cortex (IL/vPL); however, a single dose of haloperidol (1 mg/kg, i.p.) was significantly less effective. Like clozapine, remoxipride (0.3 mg/kg, i.p.) robustly increased c-fos mRNA expression in IL/vPL. Interestingly, 0.6 and 1.25 mg/kg of remoxipride were less effective than 0.3 mg/kg. These data suggest that prefrontal cortical neurons may contribute to the atypical pharmacologic profile of APDs.
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Merchant, K., Evans, D. & Figur, L. Differential Induction of c-fos mRNA in Rat Prefrontal Cortex by Typical Versus Atypical Antipsychotics. Neuropsychopharmacol 11, 276 (1994). https://doi.org/10.1038/sj.npp.1380179
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DOI: https://doi.org/10.1038/sj.npp.1380179