The comparative effects of haloperidol, (−)-sulpiride, and SCH23390 on c- fos and c- jun mRNA expressions, and AP-1 DNA binding activity

Abstract

The c- fos and c- jun mRNA expressions were measured by the RNase protection assay method following intraperitoneal injection of haloperidol, (D1 and D2 receptor antagonists), (−)-sulpiride, (D2 receptor antagonist), and SCH23390, (D1 receptor antagonist). Haloperidol and (−)-sulpiride increased their mRNA expressions in a dose-dependent manner, peaking at 30 min after injection followed by a gradual decline. The SCH23390 did not induce expression of either c- fos or c- jun mRNA. A significant decrease of c- fos as well as c- jun mRNA expression was found due to pretreatment with SCH23390 (1 mg/kg i.p.) followed by injection of (−)-sulpiride (20 mg/kg i.p.). The results suggest that the expression of these mRNAs is closely related to the dopamine D2-like antagonism. Administration of haloperidol or (−)-sulpiride increased AP-1 DNA binding activity with similar manner of dose-dependence, whereas their activities were reduced by Fos and Jun antibodies, implying that AP-1 components, transcriptional factors, forming due to Fos and Jun were actually activated by either haloperidol or (−)-sulpiride.