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Delineation of the Role of Nicotinic Acetylcholine Receptor Genes in Alcohol Preference in Mice

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Abstract

The genetic factors that increase risk for alcohol and nicotine addiction have been elusive, although the frequent co-abuse of these drugs suggests they may act on a common biological pathway. A site of action for both nicotine and alcohol effects in the brain are neuronal nicotinic acetylcholine receptors (nAChR). This report explores the association between six nAChR subunit genes (Chrna3, Chrna4, Chrnb4, Chrnb2, Chrna5, and Chrna7) with alcohol preference (AP) using co-segregation of AP with nAChR subunit genotypes in a F2 population produced from reciprocal crosses of alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) strains of mice. Polymorphisms located within the Chrna5-Chrna3-Chrnb4 cluster on mouse chromosome 9 were found to co-segregate with AP, with high-drinking F2 mice carrying B6 alleles and low-drinking F2 mice carrying D2 alleles. Further, the Chrnb4 and Chrna5 genes showed expression differences between B6 and D2 mice, which is compatible with their involvement in AP in mice and, potentially, alcohol abuse in humans.

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Acknowledgements

The results included in this report and the first draft of the manuscript were generated by MS. Additional results included were generated by JW, ED and EH. MK was responsible for finalizing the manuscript. We are grateful to Haroon Sheikh for his technical advice and Jennie Kuretzky for her lab work. This research was financially supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Institute of Health Research (CIHR), and Ontario Mental Health Foundation (OMHF) to SMS. This work was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Ontario Mental Health Foundation.

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  1. Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, ON, N6A 5B7, Canada

    Melissa N. Symons, Julia Weng, Eric Diehl, Eileen Heo, Morgan L. Kleiber & Shiva M. Singh

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  1. Melissa N. Symons
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  2. Julia Weng
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  3. Eric Diehl
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  4. Eileen Heo
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  5. Morgan L. Kleiber
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Correspondence to Shiva M. Singh.

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Edited by Stephen Maxson.

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Symons, M.N., Weng, J., Diehl, E. et al. Delineation of the Role of Nicotinic Acetylcholine Receptor Genes in Alcohol Preference in Mice. Behav Genet 40, 660–671 (2010). https://doi.org/10.1007/s10519-010-9366-9

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