Psychopharmacology

, Volume 205, Issue 4, pp 529–564 | Cite as

The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress

  • Sandeep Kumar
  • Patrizia Porcu
  • David F. Werner
  • Douglas B. Matthews
  • Jaime L. Diaz-Granados
  • Rebecca S. Helfand
  • A. Leslie Morrow
Review

Abstract

The past decade has brought many advances in our understanding of GABAA receptor-mediated ethanol action in the central nervous system. We now know that specific GABAA receptor subtypes are sensitive to ethanol at doses attained during social drinking while other subtypes respond to ethanol at doses attained by severe intoxication. Furthermore, ethanol increases GABAergic neurotransmission through indirect effects, including the elevation of endogenous GABAergic neuroactive steroids, presynaptic release of GABA, and dephosphorylation of GABAA receptors promoting increases in GABA sensitivity. Ethanol’s effects on intracellular signaling also influence GABAergic transmission in multiple ways that vary across brain regions and cell types. The effects of chronic ethanol administration are influenced by adaptations in GABAA receptor function, expression, trafficking, and subcellular localization that contribute to ethanol tolerance, dependence, and withdrawal hyperexcitability. Adolescents exhibit altered sensitivity to ethanol actions, the tendency for higher drinking and longer lasting GABAergic adaptations to chronic ethanol administration. The elucidation of the mechanisms that underlie adaptations to ethanol exposure are leading to a better understanding of the regulation of inhibitory transmission and new targets for therapies to support recovery from ethanol withdrawal and alcoholism.

Keywords

Alcohol GABAA receptor Neuroactive steroids Protein kinase C 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sandeep Kumar
    • 1
  • Patrizia Porcu
    • 1
  • David F. Werner
    • 1
  • Douglas B. Matthews
    • 3
  • Jaime L. Diaz-Granados
    • 3
  • Rebecca S. Helfand
    • 3
  • A. Leslie Morrow
    • 1
    • 2
  1. 1.Department of Psychiatry, Bowles Center for Alcohol StudiesUniversity of North Carolina School of MedicineChapel HillUSA
  2. 2.Department of Pharmacology, Bowles Center for Alcohol StudiesUniversity of North Carolina School of MedicineChapel HillUSA
  3. 3.Department of Psychology and NeuroscienceBaylor UniversityWacoUSA

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