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γ-hydroxybutyric acid (GHB) is not an agonist of extrasynaptic GABAA receptors

Citation

Connelly, WM and Errington, AC and Crunelli, V, γ-hydroxybutyric acid (GHB) is not an agonist of extrasynaptic GABAA receptors, PLoS One, 8, (11) Article e79062. ISSN 1932-6203 (2013) [Refereed Article]


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Copyright Statement

Copyright 2013 Connelly et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0079062

Abstract

γ-Hydroxybutyric acid (GHB) is an endogenous compound and a drug used clinically to treat the symptoms of narcolepsy. GHB is known to be an agonist of GABAB receptors with millimolar affinity, but also binds with much higher affinity to another site, known as the GHB receptor. While a body of evidence has shown that GHB does not bind to GABAA receptors widely, recent evidence has suggested that the GHB receptor is in fact on extrasynaptic α4β1δ GABAA receptors, where GHB acts as an agonist with an EC50 of 140 nM. We investigated three neuronal cell types that express a tonic GABAA receptor current mediated by extrasynaptic receptors: ventrobasal (VB) thalamic neurons, dentate gyrus granule cells and striatal medium spiny neurons. Using whole-cell voltage clamp in brain slices, we found no evidence that GHB (10 ÁM) induced any GABAA receptor mediated current in these cell types, nor that it modulated inhibitory synaptic currents. Furthermore, a high concentration of GHB (3 mM) was able to produce a GABAB receptor mediated current, but did not induce any other currents. These results suggest either that GHB is not a high affinity agonist at native α4β1δ receptors, or that these receptors do not exist in classical areas associated with extrasynaptic currents.

Item Details

Item Type:Refereed Article
Keywords:epilepsy, GHB, GABA receptors
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Connelly, WM (Dr William Connelly)
ID Code:131561
Year Published:2013
Web of Science® Times Cited:20
Deposited By:Medicine
Deposited On:2019-03-22
Last Modified:2019-05-01
Downloads:2 View Download Statistics

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