INDUCTION OF C-FOS MESSENGER-RNA IN RAT MEDIAL PREFRONTAL CORTEX BY ANTIPSYCHOTIC-DRUGS - ROLE OF DOPAMINE D2 AND D3 RECEPTORS

The present studies compared the effects of acute and chronic administ ration of haloperidol or clozapine on c-fos mRNA expression in the rat medial prefrontal cortex. Acute administration of clozapine, but not haloperidol, robustly increased c-fos mRNA expression in the infralimb ic and prelimbic cortex of the rat. Even though most c-fos mRNA-expres sing neurons in the clozapine- treated animals were localized in deep cortical layers, labeled neurons were found organized into several cel l bridges connecting the superficial and deep layers of the cortex. Af ter chronic treatment with clozapine, c-fos mRNA was reduced by simila r to 60% of that seen acutely; however, the columns of c-fos mRNA expr essing neurons did not show the same magnitude of tolerance. Haloperid ol had no significant effect even after chronic treatment. We examined further the role of dopamine D2 versus D3 receptors in c-fos gene ind uction in the infralimbic cortex by studying the acute effects of remo xipride and U-99194A. Remoxipride, a selective D2 antagonist in vitro, induced c-fos mRNA at very low doses and lost its ability to alter c- fos mRNA levels at higher doses. Interestingly, U-99194A, an antagonis t with 20-fold selectivity for D3 over D2 receptors, also produced gre ater induction of c-fos mRNA at lower doses. We hypothesize that block ade of D3 receptors may enhance c-fos gene expression in the medial pr efrontal cortex but that of D2 receptors may prevent the same.