The α3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation

H. M. Kamens, C. S. McKinnon, N. Li, M. L. Helms, John Belknap, Tamara Phillips

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Alcohol and nicotine are coabused, and preclinical and clinical data suggest that common genes may influence responses to both drugs. A gene 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 F2 mice were then used 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 α3 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 (α5 and β4) were not differentially expressed. Locomotor stimulation was not expressed on the genetic background of Chrna3 heterozygous (+/-) and wild-type (+/+) mice; +/- mice were more sensitive than +/+ mice to the locomotor depressant effects of ethanol. Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalGenes, Brain and Behavior
Volume8
Issue number6
DOIs
StatePublished - Aug 2009

Fingerprint

Nicotinic Receptors
Ethanol
Genes
Chromosomes, Human, Pair 9
Congenic Mice
Brain
Multigene Family
Nicotine
Alcohols
Gene Expression
Mutation

Keywords

  • Alcohol
  • Ethanol
  • Locomotor stimulation
  • Mouse
  • Nicotinic acetylcholine receptors
  • Quantitative trait locus

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

The α3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation. / Kamens, H. M.; McKinnon, C. S.; Li, N.; Helms, M. L.; Belknap, John; Phillips, Tamara.

In: Genes, Brain and Behavior, Vol. 8, No. 6, 08.2009, p. 600-609.

Research output: Contribution to journalArticle

Kamens, H. M. ; McKinnon, C. S. ; Li, N. ; Helms, M. L. ; Belknap, John ; Phillips, Tamara. / The α3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation. In: Genes, Brain and Behavior. 2009 ; Vol. 8, No. 6. pp. 600-609.
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