Amygdaloid pERK1/2 in corticotropin-releasing hormone overexpressing mice under basal and acute stress conditions

Abstract

Corticotropin-releasing hormone (CRH) coordinates neuroendocrine and behavioral adaptations to stress. Acute CRH administration in vivo activates extracellular signal-regulated kinase 1/2 (ERK1/2) in limbic brain areas, acting through the CRH receptor type 1 (CRH-R1). In the present study, we used CRH-COE-Cam mice that overexpress CRH in limbic-restricted areas, to analyze the effect of chronic CRH overexpression on ERK1/2 activation. By immunohistochemistry and confocal microscopy analysis we found that pERK1/2 levels in the basolateral amygdala (BLA) were similar in control and CRH overexpressing mice under basal conditions. Acute stress caused comparably increased levels of corticosterone in both control (CRH-COE con-Cam) and CRH overexpressing (CRH-COE hom-Cam) animals. CRH-COE hom-Cam mice after stress showed reduced pERK1/2 immunoreactivity in the BLA compared to CRH-COE hom-Cam animals under basal conditions. Radioligand binding and in situ hybridization revealed higher density of CRH-R1 in the amygdala of CRH-COE hom mice under basal conditions compared to control littermates. A significant reduction of the receptor levels was observed in this area after acute stress, suggesting that stress may trigger CRH-R1 internalization/downregulation in these CRH overexpressing mice. Chronic CRH overexpression leads to reduced ERK1/2 activation in response to acute stress in the BLA.