The Role of GABAA Receptors in Mediating the Effects of Alcohol in the Central Nervous System

Overview

Journal J Psychiatry Neurosci

Specialty Psychiatry

Date 2003 Aug 19

PMID 12921221

Citations 105

Authors

Martin Davies

Affiliations

Soon will be listed here.

Abstract

Ethanol is a chemically simple compound that produces many well-known effects in humans. The prevailing idea for many years was that ethanol and other alcohols exerted their effects on the central nervous system (CNS) by non-selectively disrupting the lipid bilayers of neurons. However, in recent years, there has been an accumulation of evidence pointing to the importance of ligand-gated ion channels (LGICs) in mediating the effects of ethanol. Of these LGICs, gamma-aminobutyric acid type A (GABAA) receptors appear to occupy a central role in mediating the effects of ethanol in the CNS. GABA is the primary inhibitory neurotransmitter in the mammalian CNS, and activation of GABAA receptors by GABA tends to decrease neuronal excitability. This article reviews several aspects of GABAA receptor and ethanol interactions, including the evidence for short- and long-term modulation of GABAA receptors by ethanol and evidence for a GABAA receptor-related genetic component of alcoholism.

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References

Barnard E, Skolnick P, Olsen R, Mohler H, Sieghart W, Biggio G . International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev. 1998; 50(2):291-313. View

Davies M, Bateson A, Dunn S . Molecular biology of the GABA(A) receptor: functional domains implicated by mutational analysis. Front Biosci. 1996; 1:d214-33. DOI: 10.2741/a127. View

Rimondini R, Sommer W, Heilig M . Effects of tiagabine and diazepam on operant ethanol self-administration in the rat. J Stud Alcohol. 2002; 63(1):100-6. View

Ye Q, Koltchine V, Mihic S, Mascia M, Wick M, Finn S . Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267. J Biol Chem. 1998; 273(6):3314-9. DOI: 10.1074/jbc.273.6.3314. View

Crabbe J, Belknap J, Mitchell S, Crawshaw L . Quantitative trait loci mapping of genes that influence the sensitivity and tolerance to ethanol-induced hypothermia in BXD recombinant inbred mice. J Pharmacol Exp Ther. 1994; 269(1):184-92. View

Holden C . Alcoholism and the medical cost crunch. Science. 1987; 235(4793):1132-3. DOI: 10.1126/science.3823872. View

Godden E, Harris R, Dunwiddie T . Correlation between molecular volume and effects of n-alcohols on human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther. 2001; 296(3):716-22. View

Anton R . Pharmacologic approaches to the management of alcoholism. J Clin Psychiatry. 2001; 62 Suppl 20:11-7. View

Gianoulakis C . Implications of endogenous opioids and dopamine in alcoholism: human and basic science studies. Alcohol Alcohol. 1996; 31 Suppl 1:33-42. View

10.

Loney E, Habbick B, Nanson J . Hospital utilization of Saskatchewan people with fetal alcohol syndrome. Can J Public Health. 1998; 89(5):333-6. PMC: 6990158. View

11.

Suzdak P, Glowa J, Crawley J, Schwartz R, Skolnick P, Paul S . A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science. 1986; 234(4781):1243-7. DOI: 10.1126/science.3022383. View

12.

Janoff A, Pringle M, Miller K . Correlation of general anesthetic potency with solubility in membranes. Biochim Biophys Acta. 1981; 649(1):125-8. DOI: 10.1016/0005-2736(81)90017-1. View

13.

Lappalainen J, Long J, Eggert M, Ozaki N, Robin R, Brown G . Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch Gen Psychiatry. 1998; 55(11):989-94. DOI: 10.1001/archpsyc.55.11.989. View

14.

OMalley S . Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse. Alcohol Alcohol. 1996; 31 Suppl 1:77-81. View

15.

Nayeem N, Green T, Martin I, Barnard E . Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis. J Neurochem. 1994; 62(2):815-8. DOI: 10.1046/j.1471-4159.1994.62020815.x. View

16.

Smith S, Gong Q, Li X, Moran M, BITRAN D, Frye C . Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated current and increases the GABAA receptor alpha4 subunit in association with increased anxiety. J Neurosci. 1998; 18(14):5275-84. PMC: 6793484. View

17.

Lovinger D . 5-HT3 receptors and the neural actions of alcohols: an increasingly exciting topic. Neurochem Int. 1999; 35(2):125-30. DOI: 10.1016/s0197-0186(99)00054-6. View

18.

WEGELIUS K, Honkanen A, Korpi E . Benzodiazepine receptor ligands modulate ethanol drinking in alcohol-preferring rats. Eur J Pharmacol. 1994; 263(1-2):141-7. DOI: 10.1016/0014-2999(94)90534-7. View

19.

Petry N . Benzodiazepine-GABA modulation of concurrent ethanol and sucrose reinforcement in the rat. Exp Clin Psychopharmacol. 1997; 5(3):183-94. View

20.

Mihic S, Liu Y, Deitrich R, Harris R . Actions of long chain alcohols on GABAA and glutamate receptors: relation to in vivo effects. Br J Pharmacol. 1996; 118(2):378-84. PMC: 1909624. DOI: 10.1111/j.1476-5381.1996.tb15413.x. View