The role of PKA in ethanol withdrawal is quite different from its roles in cannabinoid or opiate withdrawal. During ethanol withdrawal, CREB phosphorylation is decreased in the rat central and medial amygdala.115 Local microinjection of Sp-cAMPS into the central amygdala normalizes the level pCREB and attenuates the increased anxiety-like behaviors evoked by ethanol withdrawal. Conversely, microinjection of Rp-cAMPS into the central or basolateral amygdala decreases CREB phosphorylation, increases anxiety, and augments ethanol consumption. The decreased amygdala pCREB is associated with decreased expression of the anxiolytic peptide, neuropeptide Y (NPY). Levels of NPY are increased by local injections of Sp-cAMPS.119 Intracerebroventricular infusion of NPY decreases the anxiety induced by ethanol withdrawal in rats.120 In P rats subjected to repeated bouts of ethanol withdrawal, intracerebroventricular infusion of NPY decreases ethanol drinking.121 In addition to NPY, the neurotrophin BDNF (another CREB-regulated protein) reduces anxiety and drinking behavior. Infusion of BDNF antisense oligonucleotides into the central and medial amygdala, but not into the basolateral amygdala, provokes anxiety-like behavior and increases alcohol intake. Both behaviors are rescued by co-infusion of BDNF.122
