Archival Report| Volume 69, ISSUE 11, P1091-1099, June 01, 2011

Neuropeptide Y Opposes Alcohol Effects on Gamma-Aminobutyric Acid Release in Amygdala and Blocks the Transition to Alcohol Dependence


      During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory gamma-aminobutyric acid (GABA) neurons in central amygdala (CeA).


      This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naive and alcohol-dependent rats.


      Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested nondependent control animals. Neuropeptide Y decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors.


      These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotherapeutic target for the treatment of alcoholism. Gamma-aminobutyric acid neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence.

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