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

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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.

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Acknowledgments

These studies were performed with support from AA15632 and DA14241. HMK was supported by MH014276 and MRP was supported by DA00436 from the National Institutes of Health. We thank Dr. Hans Rollema for critically reading an earlier version of this manuscript.

Disclosure/conflicts of interest

MRP received a small grant from Pfizer in 2007 to study the effects of varenicline in animal models of depression. The authors have no current financial conflicts of interest to disclose.

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Correspondence to Marina R. Picciotto.

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Senior Editor: Klaus Miczek

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Kamens, H.M., Andersen, J. & Picciotto, M.R. Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice. Psychopharmacology 208, 613–626 (2010). https://doi.org/10.1007/s00213-009-1759-1

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  • DOI: https://doi.org/10.1007/s00213-009-1759-1

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