GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid


The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABAB receptors (GABABRs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABAA and GABABRs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABABR agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABABRs and mediated by Ca2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB.

Publication DOI:
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited. Funding: Wellcome Trust (091882), the MRC (G0900671) and the EU (FP7 HEALTH-F2-2007-202167).
Uncontrolled Keywords: absence seizures,baclofen,reward,thalamus,ventral tegmental area,Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all)
Publication ISSN: 1471-2970
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://rstb.roy ... 97-605a09af7f44 (Publisher URL)
PURE Output Type: Article
Published Date: 2014-10-19
Published Online Date: 2014-09-15
Authors: Gould, Timothy
Chen, Lixin
Emri, Zsuzsa
Pirttimaki, Tiina
Errington, Adam C.
Crunelli, Vincenzo
Parri, H. Rheinallt (ORCID Profile 0000-0002-1412-2688)



Version: Published Version

License: Creative Commons Attribution

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