The role of GABAA receptors in mediating the effects of alcohol in the central nervous system
- PMID: 12921221
- PMCID: PMC165791
The role of GABAA receptors in mediating the effects of alcohol in the central nervous system
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.
L'éthanol est un composé chimiquement simple qui produit de nombreux effets biens connus chez les humains. Le concept selon lequel l'éthanol et les autres alcools exercent leurs effets sur le système nerveux central (SNC) par une perturbation non sélective de la bicouche lipidique des neurones a prévalu pendant des années. En revanche, ces dernières années, une masse de données probantes ont souligné l'importance des canaux ioniques dont l'ouverture est contrôlée par un ligand (LGIC) dans la médiation des effets de l'éthanol. Au nombre des LGIC, les récepteurs de l'acide gamma-aminobutyrique de type A (GABAA) semblent jouer un rôle pivot dans la médiation des effets de l'éthanol sur le SNC. Le GABA est le principal neurotransmetteur inhibiteur dans le SNC des mammifères et l'activation par le GABA des récepteurs GABAA a tendance à diminuer l'excitabilité neuronale. Le présent article examine divers aspects des interactions entre les récepteurs GABAA et l'éthanol, y compris les données probantes sur la modulation à court et à long terme des récepteurs GABAA par l'éthanol et les données probantes sur une dimension génétique de l'alcoolisme se rattachant aux récepteurs GABAA.
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