Intravenous Self-Administration of Alcohol in Selectively Bred High- and Low- Alcohol Preferring Mice

Abstract

Genetic vulnerability to alcoholism is theorized to be caused by multiple interacting genetic loci, each with a small to modest effect combining under certain environmental influences to contribute to vulnerability to ethanol dependence. Animal models such as selectively bred rodent lines can be used to address this hypothesis of genetic vulnerability. High-drinking lines are implicitly assumed by many to be evidence of high ethanol reinforcement without consideration for variables such as differential pre- and post ingestive effects, low response to alcohol or novelty-seeking. Therefore, it is an open question as to whether animal studies support the idea that genetic differences in free-choice drinking are correlated with genetic differences in other assessments of ethanol-reinforced behavior, including those utilizing operant and classical conditioning. Thus, the present study utilizes selectively bred High- and Low- Alcohol Preferring mice tested for operant intravenous alcohol administration to address the hypothesis that High Alcohol Preferring mice would show evidence of greater alcohol reinforcement than their selectively bred opposite, Low Alcohol Preferring mice. Evidence for greater reinforcement was supported by High Alcohol Preferring mice voluntarily pressing a lever to administer an intravenous dose of alcohol in a two lever choice paradigm, administering higher doses of intravenous alcohol, and tracking the location of the active alcohol lever during a lever reversal procedure in comparison to Low Alcohol Preferring mice. This study supports the High- and Low- Alcohol Preferring mice as a useful genetic model of alcohol-related vulnerability even when utilizing a route of administration that bypasses the digestive system.