Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice

Ethanol (EtOH)‐induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of alcohol dependence, but its impact on alcohol abuse is not clear. EIBS development is dependent upon animal species, strain and also individual factors. We proposed here to decipher the co‐expression of EIBS and EtOH intake in individual animals among outbred Swiss mice, which exhibit heterogeneity that parallels what may occur in humans. To do so, mice were exposed to a two‐bottle choice with free access to water or 10% EtOH for 6 days just before and immediately after chronic intraperitoneal 2.5 g/kg ethanol injections once a day for 10 consecutive days. Based on their sensitization scores, mice were split into resistant and sensitized animals. First, we showed that individual susceptibility to EIBS is inversely correlated with voluntary EtOH consumption. Exposure to repeated EtOH during EIBS development increased subsequent EtOH intake among the entire population. Very interestingly, subsequent analyses suggested that the less the mice are sensitized the more they increase their EtOH intake; however, resistant mice were sensitive to EtOH adulteration with quinine, whereas sensitized ones maintained their EtOH intake levels, therefore exhibiting a compulsive‐like drinking pattern. In addition, we showed that resistant mice do not exhibit a weaker sensitivity to the aversive properties of EtOH that may contribute to their higher level of EtOH intake compared to sensitized mice. This study confirms and extends previous data showing a deep relationship between propensity for EtOH consumption and susceptibility to EIBS in Swiss mice. Ethanol‐induced behavioral sensitization (EIBS) may play a role in alcohol dependence, but its impact on alcohol abuse is not clear. Here we showed that outbred Swiss mice susceptibility to EIBS is inversely correlated with voluntary ethanol consumption. EIBS development increased subsequent ethanol intake and the less mice are sensitized the more they increase their ethanol intake; however, resistant mice were sensitive to ethanol adulteration with quinine, whereas sensitized ones maintained their ethanol intake levels, therefore exhibiting a compulsive‐like drinking pattern.