A role for GABA mechanisms in the motivational effects of alcohol

Biochem Pharmacol. 2004 Oct 15;68(8):1515-25. doi: 10.1016/j.bcp.2004.07.031.


Low doses of ethanol have been hypothesized to act directly via proteins that form ligand-gated receptor channels, such as the gamma-aminobutyric acid (GABA) receptor complex, to allosterically alter function, particularly in specific brain areas such as those hypothesized to be involved in ethanol reinforcement. At the pharmacological level, one can antagonize the effects of ethanol with GABA antagonists, particularly its sedative, anxiolytic-like and acute reinforcing actions. Brain sites involved in the GABAergic component of ethanol reinforcement include the ventral tegmental area, elements of the extended amygdala (including the central nucleus of the amygdala), and the globus pallidus. Chronic administration of ethanol sufficient to produce dependence and increased ethanol intake are associated with increased GABA release in the amygdala and increased sensitivity to GABA agonists. A hypothesis is proposed that GABAergic interactions with the brain stress neurotransmitter corticotropin-releasing factor in specific elements of the extended amygdala may be an important component for the motivation for excessive drinking associated with the transition from social drinking to addiction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alcoholism / metabolism*
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Central Nervous System Depressants / administration & dosage
  • Ethanol / administration & dosage*
  • GABA Agents / pharmacology
  • Prosencephalon / drug effects
  • Prosencephalon / metabolism
  • Rats
  • Reinforcement, Psychology
  • Self Administration
  • Substance Withdrawal Syndrome / metabolism
  • gamma-Aminobutyric Acid / physiology*


  • Central Nervous System Depressants
  • GABA Agents
  • Ethanol
  • gamma-Aminobutyric Acid