Schematic diagram of the effects of acute alcohol and NPY on GABAergic synaptic transmission in the medial aspect of the CeA. GABAergic afferents in the medial CeA arise largely from the lateral CeA and intercalated GABA cells, and commonly co-express NPY and/or other neuropeptides. Glutamatergic inputs to medial CeA arise largely from BLA. In this simplified scheme, GABAARs are located post-synaptically, and G-protein coupled receptors (GPCRs) that bind NPY are located both pre- (Y2) and post-synaptically (Y1). Acute alcohol promotes pre-synaptic GABA release in the medial CeA of both alcohol-naïve and alcohol-dependent rodents, perhaps via actions at CRF1Rs (not shown here). Increased GABA release produced by alcohol inhibits GABAergic output from the medial CeA, thereby leading to excitation (i.e., disinhibition) of downstream effector regions. Conversely, NPY decreases pre-synaptic GABA release in the medial CeA via actions at Y2Rs, and this effect is enhanced following a history of either alcohol dependence or alcohol binge exposure (Gilpin et al., 2011; Sparrow et al., 2012). Reduced GABA release produced by NPY disinhibits GABAergic output from the medial CeA, thereby leading to inhibition of downstream effector regions. Chronic alcohol exposure enhances many aspects of synaptic transmission in CeA (e.g., stronger effects of acute alcohol, NPY, and CRF on GABAergic transmission), perhaps due to changes in transmitter expression and/or receptor levels. Here, it is hypothresized that what may (also) be recruited during the transition to alcohol dependence is the pre-synaptic interaction of NPY & GABA and the heteroceptor function of Y2Rs. It is also conceivable that individual differences in the balance between basal autoreceptor and heteroceptor functions of Y2Rs may predict alcohol effects in CeA as well as the propensity to abuse alcohol. Based on this model, it is hypothesized that NPY regulates anxiety-like behavior (regardless of alcohol history) via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.