Cholinergic modulation of ethanol-induced stimulation

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DESCRIPTION (provided by applicant): One way to study the biological underpinnings of complex traits is to make use of simple behaviors that can predict complex traits. The use of these simple behaviors, or endophenotypes, are proving useful in understanding drug abuse and addiction. One such behavior is locomotor stimulation in response to a drug. Current evidence suggests that there is a common gene or quantitative trait locus (QTL) on chromosome 9 that influences sensitivity to cocaine, ethanol, and methamphetamine. This QTL will be confirmed with a congenic mouse strain that has a C57BL/6J region of chromosome 9 introgressed on a DBA/2J background. The role of nicotinic acetylcholine (nACh) receptors in drug induced stimulation will then be examined by using pharmacologic and molecular techniques. Specifically, the role of nACh receptors containing an a3 subunit will be examined because this represents one potential candidate gene that resides in the chromosome 9 QTL region. In addition to receptor antagonist studies, quantitative reverse transcriptasepolymerase chain reaction will be employed to examine mRNA expression and autoradiography will be used to examine receptor density differences. These data will provide evidence for the involvement of nACh receptors in drug-induced stimulation and in drug use and abuse.