| 19178568 |
Kamens HM, McKinnon CS, Li N, Helms ML, Belknap JK, Phillips TJ: The alpha3 Subunit of the Nicotinic Acetylcholine Receptor is a Candidate Gene for Ethanol Stimulation. Eur J Neurosci. 2009 Apr;29(8):1588-603.
Alcohol and nicotine are co-abused, and preclinical and clinical data suggest that common genes may influence responses to both drugs. A gene (s) in a region of mouse chromosome 9 that includes a cluster of three nicotinic acetylcholine receptor (nAChR) subunit genes influences the locomotor stimulant response to ethanol. The current studies first used congenic mice to confirm the influential gene on chromosome 9. Congenic F (2) mice were then utilized to more finely map the location. Gene expression of the three subunit genes was quantified in strains of mice that differ in response to ethanol. Finally, the locomotor response to ethanol was examined in mice heterozygous for a null mutation of the alpha3 nAChR subunit gene (Chrna3). Congenic data indicate that a gene on chromosome 9, within a 46 cM region that contains the cluster of nAChR subunit genes, accounts for 41% of the genetic variation in the stimulant response to ethanol. Greater expression of Chrna3 was found in whole brain and dissected brain regions relevant to locomotor behavior in mice that were less sensitive to ethanol-induced stimulation compared to mice that were robustly stimulated; the other two nAChR subunit genes in the gene cluster (alpha5 and beta4) were not differentially expressed. Locomotor stimulation was not expressed on the genetic background of Chrna3 heterozygous (+/-) and wildtype (+/+) mice, but +/- mice were more sensitive to the locomotor depressant effects of ethanol than +/+ mice. Chrna3 is a candidate gene for the acute locomotor response to ethanol that deserves further examination. |
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