Chronic Stress and Sex as Mediators of the Basolateral-Centromedial Amygdala Circuit and its Response to Acute Ethanol

Anxiety disorders are the most common class of mental disorders in the United States, and they both promote and exacerbate disorders of substance abuse. Mounting evidence of sex differences in the relationship between anxiety disorders and alcoholism supports the potential existence of an anxiety-dependent vulnerability to alcohol abuse in women compared with men. One potential point of overlap in the physiological systems involved in anxiety response and reward processing is the amygdala. Here, a model of chronic stress in rodents was employed to probe changes in the electrophysiological and biochemical properties of the amygdala at a post-stress baseline and during a post-stress first exposure to alcohol. Electrophysiological data revealed that neurons in the centromedial amygdala were more responsive to stimulation in the basolateral amygdala in females compared with males, but a history of chronic stress altered the female response to match that of males with or without a history of chronic stress. Protein analysis of postsynaptic glutamatergic receptor expression and phosphorylation in the amygdala did not indicate any differences based on sex or exposure to stress or alcohol. These data demonstrate a sex difference in stress-induced alterations in amygdala circuitry and indicate a potential role for this circuitry in the comorbidity of anxiety disorders and alcoholism.