Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice

Helen M. Kamens, Jimena Andersen, Marina R. Picciotto

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Rationale: 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.

Original languageEnglish (US)
Pages (from-to)613-626
Number of pages14
JournalPsychopharmacology
Volume208
Issue number4
DOIs
StatePublished - Mar 2010

All Science Journal Classification (ASJC) codes

  • Pharmacology

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