Research reportChanges in the brain expression of alpha-2 subunits of the GABA-A receptor after chronic restraint stress in low- and high-anxiety rats

•Chronic restraint stress decreased high anxiety rats (HR) activity in Porsolt test.•HR restraint rats had decreased alpha-2 GABA-A receptors density in hippocampus.•HR restraint rats had decreased alpha-2 GABA-A receptors density in prefrontal cortex.•HR restraint rats had increased alpha-2 GABA-A receptors density in basolateral amygdala.•HR restraint rats had a lower corticosterone concentration in prefrontal cortex.

This study assessed the mechanisms underlying the behavioral differences between high- (HR) and low-anxiety (LR) rats selected for their behavior in the contextual fear test (i.e., the duration of the freezing response was used as a discriminating variable). Rats were subjected to chronic restraint stress (21 days, 3 h daily). We found that in the HR group, chronic restraint stress decreased rat activity in the Porsolt test and reduced the concentration of corticosterone in the prefrontal cortex. The behavioral changes were accompanied by a lower expression of alpha-2 GABA-A receptor subunits in the secondary motor cortex (M2 area) and in the dentate gyrus of the hippocampus (DG) compared to LR restraint animals. Moreover, restraint stress increased the density of alpha-2 GABA-A subunits in the basolateral amygdala (BLA) in HR rats and decreased the expression of these subunits in the DG and M2 areas compared to the HR control group. The present results suggest that, in HR rats exposed to chronic restraint stress, the function of hippocampal and cortical GABAergic neurotransmission is attenuated and that this effect could have important influences on the functioning of the hypothalamic-pituitary-adrenal axis and on depressive symptoms.