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Deletion of the α7 Nicotinic Receptor Subunit Gene Results in Increased Sensitivity to Several Behavioral Effects Produced by Alcohol
Author(s) -
Bowers Barbara J.,
McClureBegley Tristan D.,
Keller Jason J.,
Paylor Richard,
Collins Allan C.,
Wehner Jeanne M.
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000156116.40817.a2
Subject(s) - prepulse inhibition , ethanol , nicotinic agonist , pharmacology , moro reflex , open field , chemistry , gene knockout , acetylcholine receptor , receptor , neuroscience , endocrinology , biology , biochemistry , reflex , psychology , gene , schizophrenia (object oriented programming) , psychiatry
Background: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric α7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used α7 gene knockout (null mutant) mice to evaluate the potential role of α7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. Methods: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol‐induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (α7 −/− ) and wild‐type (α7 +/+ ) mice. Results: Relative to α7 +/+ mice, α7 −/− mice were more sensitive to the activating effects of ethanol on open‐field activity, ethanol‐induced hypothermia, and duration of loss of the righting response. Deletion of the α7 gene did not influence the effects of ethanol on Y‐maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. Conclusions: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the α7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.