Opposite actions of alcohol on tonic GABA A receptor currents mediated by nNOS and PKC activity

Joshua S. Kaplan, Claudia Mohr, David J. Rossi

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The molecular mechanisms that mediate genetic variability in response to alcohol are unclear. We found that alcohol had opposite actions (enhancement or suppression) on GABA A receptor (GABA A R) inhibition in granule cells from the cerebellum of behaviorally sensitive, low alcohol-consuming Sprague-Dawley rats and DBA/2 mice and behaviorally insensitive, high alcohol-consuming C57BL/6 mice, respectively. The effect of alcohol on granule cell GABA A R inhibition was determined by a balance between two opposing effects: enhanced presynaptic vesicular release of GABA via alcohol inhibition of nitric oxide synthase (NOS) and a direct suppression of the activity of postsynaptic GABA A Rs. The balance of these two processes was determined by differential expression of neuronal NOS (nNOS) and postsynaptic PKC activity, both of which varied across the rodent genotypes. These findings identify opposing molecular processes that differentially control the magnitude and polarity of GABA A R responses to alcohol across rodent genotypes.

Original languageEnglish (US)
Pages (from-to)1783-1793
Number of pages11
JournalNature Neuroscience
Volume16
Issue number12
DOIs
StatePublished - Oct 28 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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