Deletion of the alpha7 nicotinic receptor subunit gene results in increased sensitivity to several behavioral effects produced by alcohol.
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 alpha7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used alpha7 gene knockout (null mutant) mice to evaluate the potential role of alpha7 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 (alpha7(-/-)) and wild-type (alpha7(-/-)) mice.


RESULTS
Relative to alpha7(+/+) mice, alpha7(-/-) 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 alpha7 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 alpha7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.
Bowers
Barbara J
BJ
Institute for Behavioral Genetics, University of Colorado at Boulder, 447 UCB, Boulder, CO 80309, USA. bbowers@colorado.edu
McClure-Begley
Tristan D
TD
Keller
Jason J
JJ
Paylor
Richard
R
Collins
Allan C
AC
Wehner
Jeanne M
JM
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology*; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects; D012890:Sleep / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002492:Central Nervous System Depressants; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000431:Ethanol; D009538:Nicotine