Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAA Receptors Via PKCδ Activation

Frontiers in Molecular Neuroscience
Juan ChenYi Shen

Abstract

Alcohol (ethanol, EtOH) is one of the most widely abused drugs with profound effects on brain function and behavior. GABAA receptors (GABAARs) are one of the major targets for EtOH in the brain. Temporary plastic changes in GABAARs after withdrawal from a single EtOH exposure occur both in vivo and in vitro, which may be the basis for chronic EtOH addiction, tolerance and withdrawal symptoms. Extrasynaptic δ-GABAAR endocytosis is implicated in EtOH-induced GABAAR plasticity, but the mechanisms by which the relative abundance and localization of specific GABAARs are altered by EtOH exposure and withdrawal remain unclear. In this study, we investigated the mechanisms underlying rapid regulation of extrasynaptic δ-GABAAR by a single EtOH withdrawal in cultured rat hippocampal neurons. Thirty-minutes EtOH (60 mM) exposure increased extrasynaptic tonic current (Itonic) amplitude without affecting synaptic GABAAR function in neurons. In contrast, at 30 min after withdrawal, Itonic amplitude and responsiveness to acute EtOH were both reduced. Similar results occurred in neurons with okadaic acid (OA) or phorbol 12,13-dibutyrate (PDBu) exposure. Protein kinase C (PKC) inhibition prevented the reduction of Itonic amplitude and the toler...Continue Reading

References

Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·R A HarrisJ M Wehner
Nov 26, 1998·The Journal of Biological Chemistry·R ChapellN J Leidenheimer
Apr 21, 1999·Brain Research. Brain Research Reviews·A K Mehta, M K Ticku
Jul 22, 1999·Annals of the New York Academy of Sciences·P J WhitingK A Wafford
Apr 3, 2001·Trends in Pharmacological Sciences·U RudolphH Möhler
Jul 16, 2002·Nature Neuroscience·Inger Sundstrom-PoromaaSheryl S Smith
Nov 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·M WallnerR W Olsen
Mar 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Valerie B CaraiscosBeverley A Orser
Apr 28, 2004·Trends in Neurosciences·Alexey SemyanovR Angus Silver
Aug 28, 2004·Trends in Neurosciences·Istvan Mody, Robert A Pearce
Sep 24, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Weizheng WeiIstvan Mody
Dec 23, 2004·Molecular Pharmacology·Patrick S ManganJaideep Kapur
Feb 8, 2005·Nature Neuroscience·H Jacob HancharMartin Wallner
Mar 2, 2005·Nature Reviews. Neuroscience·Mark Farrant, Zoltan Nusser
Sep 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Josef T KittlerStephen J Moss
Feb 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing LiangIgor Spigelman
Jun 27, 2007·Alcohol·Richard W OlsenMartin Wallner
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing LiangIgor Spigelman
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joseph GlykysIstvan Mody
Apr 3, 2008·Nature Reviews. Neuroscience·Tija C JacobRachel Jurd
Nov 14, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Doo-Sup ChoiRobert O Messing
Oct 14, 2010·The Journal of Biological Chemistry·Armen M AbramianStephen J Moss
Dec 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Claudia GonzalezRichard W Olsen
Oct 10, 2013·The European Journal of Neuroscience·Damian P Bright, Trevor G Smart
Jan 21, 2015·Advances in Pharmacology·Yasuko NakamuraStephen J Moss
Jan 26, 2016·Molecular and Cellular Neurosciences·David F WernerA Leslie Morrow
Feb 10, 2016·The Journal of Pharmacology and Experimental Therapeutics·Stephen L CarlsonA Leslie Morrow
Dec 22, 2017·Neuron·Karina P AbrahaoDavid M Lovinger

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