The effects of the recurrent social isolation stress on fear extinction and dopamine D(2) receptors 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 D(2) receptors (D(2)R) 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 D(2)R expression in the nuclei of the amygdala and the hippocampus (immunocytochemical technique), and mRNA levels for D(2)R 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 D(2)R in the CA1 area of the hippocampus compared to the extinguished and the control rats. In turn, the isolated group presented higher D(2)R immunoreactivity in the CA1 area compared to the extinguished, the control, and the extinguished isolated animals. Moreover, the extinguished animals had higher expression of D(2)R 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 D(2)R expression in the amygdala and hippocampus and increased expression of miRNA-128 in the amygdala. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43440-022-00430-8.