title: The β2 nicotinic acetylcholine receptor subunit differentially influences ethanol behavioral effects in the mouse.
abstract: The high co-morbidity between alcohol (ethanol) and nicotine abuse suggests that nicotinic acetylcholine receptors (nAChRs), thought to underlie nicotine dependence, may also be involved in alcohol dependence. The β2* nAChR subtype serves as a potential interface for these interactions since they are the principle mediators of nicotine dependence and have recently been shown to modulate some acute responses to ethanol. Therefore, the aim of this study was to more fully characterize the role of β2* nAChRs in ethanol-responsive behaviors in mice after acute exposure to the drug. We conducted a battery of tests in mice lacking the β2* coding gene (Chrnb2) or pretreated with a selective β2* nAChR antagonist for a range of ethanol-induced behaviors including locomotor depression, hypothermia, hypnosis, and anxiolysis. We also tested the effect of deletion on voluntary escalated ethanol consumption in an intermittent access two-bottle choice paradigm to determine the extent of these effects on drinking behavior. Our results showed that antagonism of β2* nAChRs modulated some acute behaviors, namely by reducing recovery time from hypnosis and enhancing the anxiolytic-like response produced by acute ethanol in mice. Chrnb2 deletion had no effect on ethanol drinking behavior, however. We provide further evidence that β2* nAChRs have a measurable role in mediating specific behavioral effects induced by acute ethanol exposure without affecting drinking behavior directly. We conclude that these receptors, along with being key components in nicotine dependence, may also present viable candidates in the discovery of the molecular underpinnings of alcohol dependence.
authors: Department of Pharmacology and Toxicology, Virginia Commonwealth University, MCV Campus, Box 980613, Richmond, VA 23298-0613, USA. dawsonaj2@vcu.edu
authors: Anton
authors: A
authors: Dawson
authors: Micheal F
authors: MF
authors: Miles
authors: M Imad
authors: MI
authors: Damaj
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D014151:Anti-Anxiety Agents; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D006990:Hypnosis; D007035:Hypothermia / Q000139:chemically induced; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D018680:Cholinergic Antagonists; D000431:Ethanol; D011978:Receptors, Nicotinic