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

Gould, Timothy M., Chen, Lixin, Emri, Zsuzsa, Pirttimaki, Tiina, Errington, Adam Clarke, Crunelli, Vincenzo and Parri, H. Rheinallt 2014. GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid. Philosophical Transactions of the Royal Society of London Series B - Biological Sciences 369 (1654) , 20130607. 10.1098/rstb.2013.0607

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: ventral tegmental area; thalamus; baclofen; reward; absence seizures
Publisher: Royal Society
ISSN: 0962-8436
Funders: Wellcome Trust, MRC
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 2014
Last Modified: 30 May 2019 15:31
URI: http://orca.cf.ac.uk/id/eprint/64760

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