THE COMPARATIVE EFFECTS OF HALOPERIDOL, (-)-SULPIRIDE, AND SCH23390 ON C-FOS AND C-JUN MESSENGER-RNA EXPRESSIONS, AND AP-1 DNA-BINDING ACTIVITY

The c-fos and c-jun mRNA expressions were measured by the RNase protec tion assay method following intraperitoneal injection of haloperidol, (D1 and D2 receptor antagonists), (-)-sulpiride, (D2 receptor antagoni st), and SCH23390, (D1 receptor antagonist). Haloperidol and (-)-sulpi ride increased their mRNA expressions in a dose-dependent manner, peak ing at 30 min after injection followed by a gradual decline. The SCH23 390 did not induce expression of either c-fos or c-jun mRNA. A signifi cant 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 bin ding activity with similar manner of dose-dependence, whereas their ac tivities were reduced by Fos and Jun antibodies, implying that AP-1 co mponents, transcriptional factors, forming due to Fos and Jun were act ually activated by either haloperidol or (-)-sulpiride. (C) 1997 Elsev ier Science B.V.