PARC Component 8

Research Component 8:
Using Genetic Models to Examine Variation in Impulsivity and Links with Alcoholism

Director: Suzanne Mitchell
Co-Directors: Chris Cunningham, Tamara Phillips

High levels of impulsivity are associated with a number of psychopathologies such as Attention-Deficit/Hyperactivity Disorder (ADHD), pathological gambling disorder, antisocial personality disorder, and various forms of drug abuse, including alcoholism.

The association between impulsivity and alcoholism could be attributable to one or more mechanisms acting at different periods during the lifespan. High levels of impulsivity might predict initial experimentation with alcohol and aspects of an individual’s response to alcohol that are associated with its continued use.

Alternatively, neuroadaptations to alcohol might acutely or chronically increase impulsive decision-making. Indeed, it is possible that both processes may be involved – heightened impulsivity precipitating initial use, then the actions of alcohol increasing impulsive decision-making, which may in turn increase the likelihood of alcoholism and decrease the likelihood of cessation. Data suggest genotypic differences in impulsivity, but these differences have not been widely investigated, nor has the interaction of the genetics of impulsivity with the genetics of alcoholism.

This proposal will examine these associations by assessing the genetic contribution to variations in impulsivity and the extent to which these variations exhibit genetic correlations with ethanol-related traits. To accomplish this aim, two measures of impulsivity will be obtained for 15 inbred strains of mice, for which several ethanol-related traits have already been characterized (ethanol preference and consumption, ethanol-induced taste aversion, ethanol-induced conditioned place preference, behavioral sensitization, acute and chronic ethanol withdrawal, etc.).

In addition, selected lines that differ in ethanol consumption will be assessed for measures of impulsivity. To explore ethanol’s neuroadaptive effects on level of impulsivity and interactions with genotypic differences in response to ethanol, these selected lines will be chronically exposed to ethanol and the effect on impulsivity measures will be recorded.

Together, these studies will permit identification of subsets of at-risk populations and increase our understanding of the mechanisms underlying the link between impulsivity and alcohol-related traits that may be associated with addiction..

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by Mark Rutledge-Gorman
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