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

22 Citations (Scopus)

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 - 2013

Fingerprint

GABA-A Receptors
Alcohols
gamma-Aminobutyric Acid
Rodentia
Genotype
Inbred DBA Mouse
Inbred C57BL Mouse
Nitric Oxide Synthase
Cerebellum
Sprague Dawley Rats

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Opposite actions of alcohol on tonic GABA A receptor currents mediated by nNOS and PKC activity. / Kaplan, Joshua S.; Mohr, Claudia; Rossi, David J.

In: Nature Neuroscience, Vol. 16, No. 12, 2013, p. 1783-1793.

Research output: Contribution to journalArticle

Kaplan, Joshua S. ; Mohr, Claudia ; Rossi, David J. / Opposite actions of alcohol on tonic GABA A receptor currents mediated by nNOS and PKC activity. In: Nature Neuroscience. 2013 ; Vol. 16, No. 12. pp. 1783-1793.
@article{db7ffd1f161c4dd3a90136d37e07ed52,
title = "Opposite actions of alcohol on tonic GABA A receptor currents mediated by nNOS and PKC activity",
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.",
author = "Kaplan, {Joshua S.} and Claudia Mohr and Rossi, {David J.}",
year = "2013",
doi = "10.1038/nn.3559",
language = "English (US)",
volume = "16",
pages = "1783--1793",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Opposite actions of alcohol on tonic GABA A receptor currents mediated by nNOS and PKC activity

AU - Kaplan, Joshua S.

AU - Mohr, Claudia

AU - Rossi, David J.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84888371946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888371946&partnerID=8YFLogxK

U2 - 10.1038/nn.3559

DO - 10.1038/nn.3559

M3 - Article

VL - 16

SP - 1783

EP - 1793

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 12

ER -