Investigations into the role of CREB in amygdaloid brain structures with regard to anxiety-like and alcohol-drinking behaviors have shown that CREB activity fluctuates depending on brain structures and alcohol “condition” (acute, chronic, or withdrawal). For instance, a series of studies by Pandey’s group conducted in the rat AMG clearly indicate a strong relationship between decreased CREB phosphorylation and high anxiety-like responses associated with acute withdrawal from 2-week ethanol treatment (62, 82). Decreases in CREB phosphorylation and downstream cAMP-inducible genes, including NPY in the central and medial, but not the basolateral, nuclei of the AMG, have been associated with a predisposition to both anxiety-like and excessive alcohol-drinking behaviors in alcohol-preferring rats (60, 84–86). Restoring CREB function to optimal level or enhancing NPY signaling in the central AMG prevented the onset of anxiety-like behaviors (84, 87, 88), while alcohol-associated anxiety disorders can be mimicked by pharmacological blockade of PKA in ethanol-naïve-preferring rats or non-preferring rats (60, 84). Thus, anxiety-induced downregulation of CREB function in the AMG may constitute a critical neuroadaptation central to the development and maintenance of alcohol dependence. As regards,
