LEVERAGING SELECTIVELY BRED MOUSE MODELS TO EXPLORE THE GENETIC RELATIONSHIPS BETWEEN ALCOHOL DRINKING, ALCOHOL SENSITIZATION, AND COCAINE SENSITIZATION.

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Boehm II SL1,2, Fritz BM1, Linsenbardt DN1

1Department of Psychology, Indiana University – Purdue University Indianapolis, Indianapolis, IN, USA
2Indiana Alcohol Research Center, Indiana School of Medicine, Indianapolis, IN, USA

Propensity to development sensitization to the locomotor stimulant effects of alcohol is believed to be a heritable risk factor for the development of alcohol use disorders in humans, and cross-sensitization between the locomotor stimulant effects of alcohol and the psychomotor stimulant cocaine have been observed in mice. However, few studies have explored the genetic relationships between alcohol drinking, alcohol sensitization, and development of cocaine sensitization. The current work leveraged mouse lines selectively bred to differ in alcohol drinking or sensitization to determine the strength of these relationships. Selective breeding results in the homozygous fixation of alleles that influence the trait of interest, in this case alcohol drinking or sensitization. When lines bred to differ on one trait are also shown to differ on a second trait, the implication is that some of the same alleles influence both the traits, and that the traits therefore share common genetic influence. The current selectively bred mouse data provides mixed results on whether alcohol drinking, alcohol sensitization, and cocaine sensitization share common genetic influence. The HAP and LAP selectively bred lines were bred for high and low two-bottle choice alcohol preference drinking, respectively (Grahame et al., 1999). In moderate support of the above relationship, HAP mice appear to develop greater sensitization to both alcohol and cocaine. However, the relationship is not supported in mice selectively bred for high (HLS) and low (LLS) development of locomotor sensitization to alcohol (Linsenbardt and Boehm, 2013); HLS and LLS mice do not appear to differ in limited-access alcohol intake, nor do they differ in development of cocaine sensitization. The current results will be discussed in the context of the specific behavioral paradigms employed, production of subsequent (replicate) selected lines, and the current literature.
This work was supported by grant AA016789 and the Indiana Alcohol Research Center.

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