The effects of the recurrent social isolation stress on fear extinction and dopamine D2 receptors in the amygdala and the hippocampus

Abstract

Background The present study assessed the influence of recurrent social isolation stress on the aversive memory extinction and dopamine D2 receptors (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.

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

“…This suggests that an optimal level of D 2 ‐like receptor signalling in the amygdala is necessary for the expression of fear. Furthermore, D 2 receptor expression may be elevated in the amygdala during extinction training (Madsen et al, 2017; Wisłowska‐Stanek et al, 2023; Table S4). Activation of Gs‐DREADDs expressed on D 2 ‐expressing central amygdala neurons before extinction training disrupted extinction recall (McCullough et al, 2018) probably by counteracting the D 2 receptor‐mediated G i cascades.…”

The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation

“…The highest regional correlations in D2 were observed during adolescence. This may reflect alterations in the relative amounts of D2 across the brain in this period, a period where D2 expression levels are prone to dynamic changes in response to stressful events [53][54][55] . D1 and D2 cell densities typically declined from P17 onwards in most regions, indicating pruning of dopamine receptors in this period.…”