Assessing initial/early aversion-resistant drinking across male and female alcohol-preferring and non-preferring rats

Abstract

Background: One trait of alcohol use disorder (AUD) is continuing to drink despite negative consequences. The current study investigated initial/early aversion-resistant drinking (ARD) across selectively bred alcohol-preferring lines to assess aversion resistance with minimal ethanol history and subsequent ethanol-seeking and drinking profiles. Additionally, ARD was assessed in alcohol-preferring and non-preferring rats using a sucrose reinforcer to determine if ARD may be a genetic risk factor for AUD. Methods: Male and female alcohol-preferring rats were given four concentrations of quinine (0.03, 0.10, 0.30, and 1.00 g/L-in random order) in an ethanol solution in the homecage for 30 min daily across 12 days. Seeking and drinking were then assessed in the operant chambers. Additional groups of alcohol-preferring and non-preferring rats were given access to the same concentrations of quinine-adulterated sucrose using the same daily, random-order presentation. Results: In ethanol, all preferring lines performed similarly, showing resistance to quinine at the lowest concentration. In the homecage, high-alcohol-drinking (HAD)1 rats drank high levels of ethanol similar to alcohol-preferring (P) rats, whereas in an operant task were more similar to the HAD2 rats. In sucrose, P and HAD2 rats were shown to be aversion resistant at low concentrations of quinine compared to baseline. Overall, the non-preferring lines all demonstrated sensitivity to quinine-adulterated sucrose. Conclusions: This study demonstrates alcohol-preferring lines show similar ARD when ethanol is the reinforcer. Regarding motivated responding, P rats show high-seeking and drinking behaviors as previously observed. In the homecage, HAD1 rats drink similarly to P rats indicating that different conditions (i.e., free vs. operant access) influence drinking behaviors between these lines. Importantly, in a sucrose reinforcer, alcohol-preferring rats are more aversion-resistant than non-preferring lines, while non-preferring lines show high sensitivity to aversion, suggesting an overall tendency to demonstrate a low level of compulsive behavior.