Chronic treatment with certain antipsychotic drugs preserves upregulation of regulator of G-protein signalling 2 mRNA in rat striatum as opposed to c-fos mRNA.

Quantitative in situ hybridization on rat coronal brain sections with radiolabelled oligonucleotide probes was performed to investigate the effects of antipsychotic drugs on mRNA levels of regulator of G-protein signalling (RGS) 2 and c-fos. This study demonstrated a similar increase of RGS2 mRNA level in the striatum upon both a single and a 21-day treatment with either haloperidol (2 mg/kg) or risperidone (7.5 mg/kg) in contrast to clozapine (20 mg/kg). Otherwise, the acute c-fos mRNA induction in the striatum was abolished by 74 to 89% upon chronic treatment with either haloperidol or risperidone. In conclusion, the induction of RGS2 mRNA in the striatum, in contrast to the immediate early gene c-fos mRNA, is preserved upon chronic treatment with haloperidol and risperidone.

Different regulation of RGS2 mRNA by haloperidol and clozapine.

Expression of RGS2 mRNA was transiently up-regulated in rat striatum (25% in the medial part and 50% in the lateral part), in contrast to cingulate cortex and lateral septum, 30 min after acute treatment with haloperidol (2 mg/kg, i.p.). This effect disappeared 24 hours post-drug treatment, similar to the acute and strong up-regulation (700% at 30 min) of c-fos mRNA. RGS3, 5, 6, 8 or 9 mRNAs were not affected. Clozapine (20 mg/kg, i.p.) at an approximately equivalent dose of D2 receptor occupancy in the striatum did not significantly affect RGS and c-fos mRNAs levels. We suggest that RGS2 mRNA expression may be differently up-regulated in a region-specific manner by antipsychotics.