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 p

SUBMITTER: Kaplan JS 

PROVIDER: S-EPMC4022289 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature