Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice.
BACKGROUND
Alcohol and nicotine are commonly co-abused. Genetic correlations between responses to these drugs have been reported, providing evidence that common genes underlie the response to alcohol and nicotine. Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system are important in mediating nicotine response, and several studies suggest that alcohol may also interact with these nAChRs.


OBJECTIVE
The aim of this study was to examine the role of nAChRs containing α7 or β2 subunits in ethanol consumption.


METHODS
A two-bottle choice paradigm was used to determine ethanol consumption in wild-type and nAChR subunit knockout mice. Challenge studies were performed using the α4β2 nAChR partial agonist varenicline.


RESULTS
Mice lacking the β2 subunit consumed a similar amount of ethanol compared to their wild-type siblings in an ethanol-drinking paradigm. In contrast, mice lacking the α7 nAChR receptor subunit consumed significantly less ethanol than wild-type mice but consumed comparable amounts of water, saccharin, and quinine. In C57BL/6J mice, varenicline dose-dependently decreased ethanol consumption with a significant effect of 2 mg/kg, without affecting water or saccharin consumption. This effect of varenicline was not reversed in mice lacking either the α7 or β2 subunit, providing evidence that nAChRs containing one of these subunits are not required for this effect of varenicline.


CONCLUSIONS
This study provides evidence that α7 nAChRs are involved in ethanol consumption and supports the idea that pharmacological manipulation of nAChRs reduces ethanol intake. Additional nAChRs may also be involved in ethanol intake, and there may be functional redundancy in the nicotinic control of alcohol drinking.
Kamens
Helen M
HM
Department of Psychiatry, School of Medicine, Yale University, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Andersen
Jimena
J
Picciotto
Marina R
MR
D000428:Alcohol Drinking / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D011810:Quinoxalines / Q000494:pharmacology* / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics*; D000068580:Varenicline; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D000068580:Varenicline; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse