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K v7 channels in the nucleus accumbens are altered by chronic drinking and are targets for reducing alcohol consumption
Author(s) -
McGuier Natalie S.,
Griffin William C.,
Gass Justin T.,
Padula Audrey E.,
Chesler Elissa J.,
Mulholland Patrick J.
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12279
Subject(s) - nucleus accumbens , medicine , pharmacology , drug , addiction , neuroscience , psychiatry , psychology , central nervous system
Alcohol use disorders ( AUDs ) are a major public health issue and produce enormous societal and economic burdens. Current F ood and D rug A dministration ( FDA )‐approved pharmacotherapies for treating AUDs suffer from deleterious side effects and are only effective in a subset of individuals. It is therefore essential to find improved medications for the management of AUDs . Emerging evidence suggests that anticonvulsants are a promising class of drugs for treating individuals with AUDs . In these studies, we used integrative functional genomics to demonstrate that genes that encode K v7 channels (i.e. K cnq 2/3) are related to alcohol (ethanol) consumption, preference and acceptance in rodents. We then tested the ability of the FDA ‐approved anticonvulsant retigabine, a K v7 channel opener, to reduce voluntary ethanol consumption of W istar rats in a two‐bottle choice intermittent alcohol access paradigm. Systemic administration and microinjections of retigabine into the nucleus accumbens significantly reduced alcohol drinking, and retigabine was more effective at reducing intake in high‐ versus low‐drinking populations of W istar rats. Prolonged voluntary drinking increased the sensitivity to the proconvulsant effects of pharmacological blockade of K v7 channels and altered surface trafficking and SUMO ylation patterns of K v7.2 channels in the nucleus accumbens. These data implicate K cnq 2/3 in the regulation of ethanol drinking and demonstrate that long‐term drinking produces neuroadaptations in K v7 channels. In addition, these results have identified retigabine as a potential pharmacotherapy for treating AUDs and K v7 channels as a novel therapeutic target for reducing heavy drinking.