Prevention of chronic immobilization stress-induced enhanced expression of glucocorticoid receptors in the prefrontal cortex by inactivation of basolateral amygdala

Abstract

Repeated exposure to stress precipitates anxiety, depression and cognitive deficits. Stress-induced activation of the hypothalamus-pituitary-adrenal (HPA) axis is modulated by the prefrontal cortex (PFC) and basolateral amygdala (BLA). It is well established that BLA positively regulates the HPA axis and undergoes hypertrophy following chronic immobilization stress (CIS). However, it is not known whether inactivation of the BLA can modulate the stress-induced changes in the expression of glucocorticoid receptors (GRs) in the PFC. To address this, we stereologically estimated GR⁺ cell densities in the prelimbic (PrL) and anterior cingulate cortex (ACC). Following ibotenate lesioning of the BLA, rats were subjected to CIS and GR⁺ cell densities were assessed. CIS increases the GR⁺ cell densities in PrL and ACC. BLA lesion prior to CIS abolished the CIS-induced increase in GR⁺ cell densities in both regions. In the second part of experiments, we evaluated whether selective inactivation of BLA during CIS would mimic the effects of BLA lesion. Interestingly, the BLA inactivation specifically during CIS prevented the increase in GR⁺ cell densities in the PrL and ACC. The findings of our study suggest that BLA regulates the stress-induced increase in prefrontal GR expression, which might be crucial in the emergence of affective and cognitive symptoms following stress. We speculate that modulation of BLA during stress might prevent HPA axis dysfunctions and GR resistance in stress-related disorders, and could assist in the development of novel therapeutic strategies to treat stress and associated disorders like depression. Further, molecular studies are warranted for the understanding of stress-induced GR resistance and its prevention via BLA inactivation.

Keywords: Anterior cingulate cortex; Chronic immobilization stress; Glucocorticoid receptors; Inactivation of basolateral amygdala; Prelimbic cortex; Unbiased stereology.