In:
Alcoholism: Clinical and Experimental Research, Wiley, Vol. 37, No. 4 ( 2013-04), p. 655-662
Abstract:
Alcohol use disorders ( AUD s) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUD s. The neuronal nicotinic acetylcholine receptors ( nAChR s) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Methods Here, we evaluate the role of the α5* nAChR for ethanol ( E t OH )‐mediated behaviors using male α5+/+ and α5−/− transgenic mice. We characterized the effect of hypnotic doses of E t OH and investigated drinking behavior using an adapted drinking‐in‐the‐dark ( DID ) paradigm that has been shown to induce high E t OH consumption in mice. Results We found the α5 subunit to be important in mediating the sedative effects of E t OH . The α5−/− mice showed slower recovery from E t OH ‐induced sleep, as measured by loss of righting reflex. Additionally, the α5−/− mice showed enhanced impairment to E t OH ‐induced ataxia. We found the initial sensitivity to E t OH and E t OH metabolism to be similar in both α5+/+ and α5−/− mice. Hence, the enhanced sedation is likely due to a difference in the acute tolerance of E t OH in α5−/− mice. However, the α5 subunit did not play a role in E t OH consumption for E t OH concentrations ranging from 5 to 30% using the DID paradigm. Additionally, varenicline was effective in reducing E t OH intake in α5−/− mice. Conclusions Together, our data suggest that the α5 nAChR subunit is important for the sedative effects of E t OH but does not play a role in E t OH consumption in male mice. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.
Type of Medium:
Online Resource
ISSN:
0145-6008
,
1530-0277
DOI:
10.1111/acer.2013.37.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2046886-6
detail.hit.zdb_id:
3167872-5
SSG:
15,3
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