Risperidone regulates dopamine D2-like receptors expression in rat brain in a time-dependent manner

Abstract

Background and Objectives: Antipsychotics can elicit dopamine supersensitivity by up-regulation of D2-like receptors (DRD2, DRD3, and DRD4) expression. Nevertheless, the expression profile of dopamine D2-like receptors in different brain regions and peripheral blood mononuclear cells (PBMCs), and changes following risperidone administration were still unclear. In this study, we would investigate the expression of D2-like receptors mRNA in different brain regions and the peripheral blood mononuclear cells (PBMCs) in rats after 2, 6 weeks risperidone administration. Methods: The experimental rats were given risperidone (0.25mg/kg/day, i.p.), and the control rats were given 0.9% NaCl. The rats were sacrificed at 0 week, 2 weeks and 6 weeks after the drug administration. Expression of the dopamine D2-like receptors was quantified by Real-time PCR method. Results: Dopamine D2-like receptors expressed in all the examined regions of rat brain. Their expression significantly increased 2weeks after risperidone administration in different brain regions. However, the changed expression of DRD2 and DRD3 turned back to the basal level 6weeks later, while the increased DRD4 expression remained in left parietal cortex. Meanwhile, DRD2 and DRD3 but not DRD4 expressed in PBMCs, however, the risperidone could not affect their expression. Conclusions: The risperidone could change the dopamine D2-like receptors expression in a time-dependent manner in different brain regions, which might guide the clinical use in the near future.