title: Neuropeptide Y opposes alcohol effects on gamma-aminobutyric acid release in amygdala and blocks the transition to alcohol dependence.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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 Y(2) receptors.
  
  
  CONCLUSIONS
  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.
authors: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, USA. nickg@scripps.edu
authors: Nicholas W
authors: NW
authors: Gilpin
authors: Kaushik
authors: K
authors: Misra
authors: Melissa A
authors: MA
authors: Herman
authors: Maureen T
authors: MT
authors: Cruz
authors: George F
authors: GF
authors: Koob
authors: Marisa
authors: M
authors: Roberto
mesh_terms: D019973:Alcohol-Related Disorders / Q000209:etiology / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D000431:Ethanol; D005680:gamma-Aminobutyric Acid