Search resultsA conceptualization of integrated actions of ethanol contributing to its GABAmimetic profile: A commentary
Title
A conceptualization of integrated actions of ethanol contributing to its GABAmimetic profile: A commentary
Publication type
Journal Article
Year of Publication
2005
Authors
Journal
Neuropsychopharmacology
Volume
30
Issue
8
Pagination
1407 - 1425
Date published
2005
ISBN
0893133X (ISSN)
Keywords
4 aminobutyric acid, 4 aminobutyric acid A receptor, 4 aminobutyric acid B receptor, 4 aminobutyric acid receptor stimulating agent, 4 aminobutyric acid release, alcohol, Animals, benzodiazepine receptor, bicuculline, Brain, brain electrophysiology, BZD-insensitive receptors, Central Nervous System Depressants, drug antagonism, Drug Interactions, drug potentiation, Ethanol, Evoked IPSCs, excitatory postsynaptic potential, GABA Agonists, GABA release, GABAergic system, GABAergic transmission, gamma-Aminobutyric Acid, Glutamate release, human, Humans, in vitro study, in vivo study, mIPSPs, Models, Biological, muscimol, nerve ending, neurosteroid, Neurosteroids, nonhuman, Phosphorylation, postsynaptic receptor, priority journal, protein function, protein localization, protein phosphorylation, protirelin derivative, Receptors, GABA, review
Abstract
Early behavioral investigations supported the contention that systemic ethanol displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in vivo electrophysiological studies implicated a regionally specific action of ethanol on GABA function. While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABAA receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention. Nonetheless, subsequent work identified GABAA receptor subtypes, with limited distribution in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In view of these data, it is hypothesized that the GABAmimetic profile for ethanol is due to activation of mechanisms associated with GABA function, distinct from a direct action on the majority of postsynaptic GABAA receptors. The primary action proposed to account for ethanol's regional specificity on GABA transmission is its ability to release GABA from some, but not all, presynaptic GABAergic terminals. As systemic administration of ethanol increases neuroactive steroids, which can enhance GABA responsiveness, this elevated level of neurosteroids is proposed to magnify the effect of GABA released by ethanol. Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABAB and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone. Thus, an integration of these consequences induced by ethanol is proposed to provide a logical basis for its in vivo GABAmimetic profile.