Helen Kamens

Behavioral Neuroscience

Helen M. Kamens, Na Li, Amy J. Eshleman, & Tamara J. Phillips

Evaluation of the alpha 3 subunit of the nicotinic acetylcholine receptor as a candidate gene for ethanol-induced locomotor activation

Abstract: Alcohol and nicotine are commonly co-abused drugs. Genetic

correlations have been reported between the responses to these drugs

in both human and animal models, suggesting that common genes may

underlie the response to both drugs. There is evidence that a gene

resides on mouse chromosome 9 that accounts for some of the phenotypic

variance in the acute locomotor response to ethanol. One gene that

resides in this area is the alpha 3 subunit of the nicotinic

acetylcholine receptor (Chrna3). Since acetylcholine

receptors are important in the behavioral response to nicotine, we

used pharmacology, gene expression, and protein expression assays to

determine if this gene is important in ethanol-induced locomotor

stimulation. We first confirmed the presence of a gene on chromosome 9

using DBA/2J mice and congenic mice that possessed C57BL/6J alleles

from 9 – 61 cM on a DBA/2J background. Mecamylamine, a nonspecific

nicotinic acetylcholine antagonist, was able to block the acute

stimulant response to ethanol. Congenic mice expressed significantly

greater Chrna3  mRNA compared to the DBA/2J control strain,

but this did not appear to translate into differences in the amount of

alpha 3 containing nicotinic receptors as measured by receptor

binding. These data provide evidence for the involvement of nicotinic

acetylcholine receptors in ethanol-induced stimulation, but it remains

unclear whether the Chrna3 gene is the quantitative trait

gene on chromosome 9.