Behavioral Endophenotypes for Differential Ethanol-Seeking and Drinking

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Project Summary: Behavioral Endophenotypes for Differential Ethanol-Seeking and Drinking (BESD) A body of findings from the I-ARC converges in suggesting that the selected lines of alcohol preferring rodents represent different genetic and behavioral models of alcoholism risk. While both the P and HAD2 rats are high drinkers, only P rats show poor impulse control and extreme ethanol (EtOH)-seeking behaviors (Beckwith & Czachowski, 2014; 2016). New preliminary data further show that EtOH naïve P rats also differ from HAD2 rats in their rapid habit formation for a non-EtOH reinforcer (persistent seeking of a novel flavored solution, even after its devaluation). Conceptually, habit formation indicates a general decreased attention to the outcomes of behavior while drinking despite adverse consequences (aversion-resistant drinking; ARD) indicates insensitivity specifically to aversive stimuli paired with reinforcement, and both are types of behavioral inflexibility. With regard to ARD, when EtOH consumption itself becomes insensitive to aversive consequences, individuals may be at risk for developing more extreme, compulsive drinking. There is thus a critical need to understand the varied behavioral and neurobiological paths by which ARD develops.  The central hypothesis of this proposal is that there are different genetic and behavioral paths to compulsive drinking and our long-term goal is to understand the relationship between behavioral inflexibility and EtOH- seeking and drinking in order to develop pharmacological interventions that target the risky phenotypes as a way to control or prevent compulsive drinking. The objectives of this application are to: 1) expand the identification of the unique risk endophenotypes to habit formation and ARD in the selected rat lines in both sexes, and 2) determine the differences in functionality of the underlying neural circuity of these genetic lines and behaviors.  The positive impact of our proposed work is the capacity to understand the genetic, behavioral, and neurobiological factors that contribute to the development of ARD, when alcoholism becomes harder to treat. By understanding these factors, we can better understand how to develop appropriate interventions.