LAUSR

Abstract Background Impaired intracellular trafficking has been proposed as a new key pathophysiology for neuropsychiatric disorders. The present study investigated the effects of risperidone on the mRNA levels of various proteins involved in intracellular trafficking, and dopaminergic receptors [long and short forms of the dopamine receptor D2 (DRD2) and dopamine receptor D1 (DRD1)] in several key brain regions of wild type adult mice exposed to social defeat stress. Methods C57BL/6J mice were subjected to chronic social defeat procedure for 10 consecutive days. The defeated mice were categorized into unsusceptible (UNS) and susceptible (SUS) groups based on performance in the social avoidance test. Animals were randomly divided into two groups, vehicle (VEH) and drug (DRUG) groups. Risperidone (RIS) was administered to the DRUG group at the dosage of 0.2 mg/kg, i.p. for 7days. After sacrifice and brain extraction, prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were obtained. The mRNA levels of our target genes were measured by real time- PCR. Results In the VEH group, mRNA expression levels of GASP1 and ARF6 were decreased in the PFC and HIP, and AMY of UNS mice respectively compared to control mice. The mRNA expression of Rab4 was rather increased in the PFC of UNS mice compared to control mice. In the DRUG group, only mRNA expression level of GASP1 was decreased in the PFC of UNS mice compared to control mice. Discussion Our results indicate that social defeat stress induces changes in expression levels of GASP1, ARF6 and Rab4 in several key brain regions and these effects are blocked by risperidone. It may suggest that risperidone can prevent or treat an impairment of intracellular trafficking caused by defeat stress. As ARF6 is known to mediate recycling of D2 receptors and GASP-1 is involved in the lysosomal sorting of D2 receptor, our findings should be discussed with regard to the changes of mRNA expression levels of DRD2 and DRD1.