1. Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice.
- Author
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Dawson A, Wolstenholme JT, Roni MA, Campbell VC, Jackson A, Slater C, Bagdas D, Perez EE, Bettinger JC, De Biasi M, Miles MF, and Damaj MI
- Subjects
- Alcohol Drinking psychology, Animals, Anxiety chemically induced, Anxiety metabolism, Central Nervous System Depressants blood, Choice Behavior drug effects, Choice Behavior physiology, Conditioning, Psychological drug effects, Conditioning, Psychological physiology, Ethanol blood, Hypnotics and Sedatives blood, Hypnotics and Sedatives pharmacology, Hypothermia chemically induced, Hypothermia metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, Motor Activity drug effects, Motor Activity physiology, Receptors, Nicotinic genetics, Reflex drug effects, Reflex physiology, Spatial Behavior drug effects, Spatial Behavior physiology, Alcohol Drinking metabolism, Central Nervous System Depressants pharmacology, Ethanol pharmacology, Receptors, Nicotinic deficiency, Reward
- Abstract
Evidence suggests that there is an association between polymorphisms in the α5 nicotinic acetylcholine receptor (nAChR) subunit and risk of developing alcohol dependence in humans. The α5 nAChR subunit has also recently been shown to modulate some of the acute response to ethanol in mice. The aim of the current study was to further characterize the role of α5-containing (α5*) nAChRs in acute ethanol responsive behaviors, ethanol consumption and ethanol preference in mice. We conducted a battery of tests in male α5 knockout (KO) mice for a range of ethanol-induced behaviors including hypothermia, hypnosis, and anxiolysis. We also investigated the effects of α5* nAChR on ethanol reward using the Conditioned Place Preference (CPP) assay. Further, we tested the effects of gene deletion on drinking behaviors using the voluntary ethanol consumption in a two-bottle choice assay and Drinking in the Dark (DID, with or without stress) paradigm. We found that deletion of the α5 nAChR subunit enhanced ethanol-induced hypothermia, hypnosis, and an anxiolytic-like response in comparison to wild-type controls. The α5 KO mice showed reduced CPP for ethanol, suggesting that the rewarding properties of ethanol are decreased in mutant mice. Interestingly, Chrna5 gene deletion had no effect on basal ethanol drinking behavior, or ethanol metabolism, but did decrease ethanol intake in the DID paradigm following restraint stress. Taken together, we provide new evidence that α5 nAChRs are involved in some but not all of the behavioral effects of ethanol. Our results highlight the importance of nAChRs as a possible target for the treatment of alcohol dependence., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2018
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