DIFFERENTIAL-EFFECTS OF CLOZAPINE AND HALOPERIDOL ON DOPAMINE-RECEPTOR MESSENGER-RNA EXPRESSION IN RAT STRIATUM AND CORTEX

The regulation of the dopamine (DA) receptors is of considerable inter est, in part because treatment with antipsychotic drugs is known to up regulate striatal D-2-like receptors. While previous studies have focu sed on the regulation of striatal DA receptors, less is known about th e pharmacological regulation of cortical DA receptors. The purpose of this study was to examine the regulation of DA mRNA receptor expressio n in the cortex compared to the striatum following treatment with anti psychotic agents. Adult male Sprague-Dawley rats were injected daily w ith haloperidol (2 mg/kg/day), clozapine (20 mg/kg/day) or a control v ehicle for a period of 14 days. Following treatment, brains were subje cted to in situ hybridization for the mRNAs encoding the five dopamine receptors; only D-1, D-2, and D-3 receptor mRNAs were detected in the se regions. Haloperidol tended to either modestly upregulate or have n o effect on dopamine receptor mRNAs detected in striatal structures, w hile clozapine generally downregulated these mRNAs. On the other hand, in the cortex, both drugs had striking effects on D-1 and D-2 mRNA le vels. Cortical D-1 mRNA was upregulated by haloperidol, but this effec t was primarily restricted to cingulate cortex; clozapine also upregul ated D-1 mRNA, but primarily in parietal regions. Haloperidol downregu lated D-2 mRNA in the majority of cortical regions, but most dramatica lly in frontal and cingulate regions; clozapine typically upregulated this mRNA, but primarily in regions other than frontal and cingulate c ortex. These results indicate that clozapine and haloperidol each have regionally-specific effects, and differentially regulate dopamine rec eptor mRNA expression in striatal and cortical regions of the rat brai n.