The effects of the recurrent social isolation stress on fear extinction and dopamine D2receptors in the amygdala and the hippocampus

Background: The present study assessed the influence of recurrent social isolation stress on the aversive memory extinction and dopamine D₂receptors (D₂R) expression in the amygdala and the hippocampus subnuclei. We also analyzed the expression of epigenetic factors potentially associated with fear extinction: miRNA-128 and miRNA-142 in the amygdala. Methods: Male adult fear-conditioned rats had three episodes of 48 h social isolation stress before each fear extinction session in weeks intervals. Ninety minutes after the last extinction session, the D₂R expression in the nuclei of the amygdala and the hippocampus (immunocytochemical technique), and mRNA levels for D₂R in the amygdala were assessed (PCR). Moreover, we evaluated the levels of miRNA-128 and miRNA-142 in the amygdala. Results: It was found that recurrent social isolation stress decreased the fear extinction rate. The extinguished isolated rats were characterized by higher expression of D₂R in the CA1 area of the hippocampus compared to the extinguished and the control rats. In turn, the isolated group presented higher D₂R immunoreactivity in the CA1 area compared to the extinguished, the control, and the extinguished isolated animals. Moreover, the extinguished animals had higher expression of D₂R in the central amygdala than the control and the extinguished isolated rats. These changes were accompanied by the increase in miRNA-128 level in the amygdala in the extinguished isolated rats compared to the control, the extinguished, and the isolated rats. Moreover, the extinguished rats had lower expression of miRNA-128 compared to the control and the isolated animals. Conclusions: Our results suggest that social isolation stress impairs aversive memory extinction and coexists with changes in the D₂R expression in the amygdala and hippocampus and increased expression of miRNA-128 in the amygdala.