A translational rodent model of individual differences in sensitivity to the aversive properties of ethanol

BackgroundA strong relationship exists between individual sensitivity to the aversive properties of ethanol and risk for alcohol use disorder (AUD). Despite this, our understanding of the neurobiological mechanisms underlying the subjective response to ethanol is limited. A major contributor to this lack of knowledge is the absence of preclinical models that enable exploration of this individual variability such as is possible in studies of humans.MethodsAdult male and female Long-Evans rats were trained to associate a novel tastant (saccharin) with acute exposure to either saline or ethanol (1.5 g/kg or 2.0 g/kg i.p.) over three conditioning days using a standard conditioned taste aversion (CTA) procedure. Variability in sensitivity to ethanol-induced CTA was phenotypically characterized using a median split across the populations studied.ResultsWhen examining group averages, both male and female rats exposed to saccharin paired with either dose of ethanol exhibited lower saccharin intake relative to saline controls indicative of ethanol-induced CTA. Examination of individual data revealed a bimodal distribution of responses uncovering two distinct phenotypes present in both sexes. CTA-sensitive rats exhibited a rapid and progressive reduction in saccharin intake with each successive ethanol pairing. In contrast, saccharin intake was unchanged or maintained after an initial decrease from baseline levels in CTA-resistant rats. While CTA magnitude was similar between male and female CTA-sensitive rats, among CTA-resistant animals females were more resistant to the development of ethanol-induced CTA than males. Phenotypic differences were not driven by differences in baseline saccharin intake.ConclusionsThese data parallel work in humans by revealing individual differences in sensitivity to the aversive properties of ethanol that emerge immediately after initial exposure to ethanol in both sexes. This model can be used in future studies to investigate the neurobiological mechanisms that confer risk for AUD.