Browsing by Subject "Compulsive drinking"

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    Assessing initial/early aversion-resistant drinking across male and female alcohol-preferring and non-preferring rats
    (Wiley, 2025) Haines, Kari M.; Smith, Nicholle E; Czachowski, Cristine L.; Psychology, School of Science
    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.
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    Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats
    (MDPI, 2022-08-05) Katner, Simon N.; Sentir, Alena M.; Steagall, Kevin B.; Ding, Zheng-Ming; Wetherill, Leah; Hopf, Frederic W.; Engleman, Eric A.; Psychiatry, School of Medicine
    With the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chronic intake, and animals, such as humans with AUD, continue drinking despite aversive consequences. Further, since there is a heritable component to AUD risk, some work has focused on genetically-selected, EtOH-preferring rodents, which could help uncover critical mechanisms driving pathological intake. In this regard, aversion-resistant drinking (ARD) takes >1 month to develop in outbred Wistar rats (and perhaps Sardinian-P EtOH-preferring rats). However, ARD has received limited study in Indiana P-rats, which were selected for high EtOH preference and exhibit factors that could parallel human AUD (including front-loading and impulsivity). Here, we show that P-rats rapidly developed compulsion-like responses for EtOH; 0.4 g/L quinine in EtOH significantly reduced female and male intake on the first day of exposure but had no effect after one week of EtOH drinking (15% EtOH, 24 h free-choice paradigm). Further, after 4−5 weeks of EtOH drinking, males but not females showed resistance to even higher quinine (0.5 g/L). Thus, P-rats rapidly developed ARD for EtOH, but only males developed even stronger ARD with further intake. Finally, rats strongly reduced intake of quinine-adulterated water after 1 or 5 weeks of EtOH drinking, suggesting no changes in basic quinine sensitivity. Thus, modeling ARD in P-rats may provide insight into mechanisms underlying genetic predispositions for compulsive drinking and lead to new treatments for AUDs.