Haines Kari M, Smith Nicholle E, Czachowski Cristine L
Addiction Neuroscience, Department of Psychology, Indiana Alcohol Research Center, Indiana University Indianapolis, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Feb;49(2):476-487. doi: 10.1111/acer.15518. Epub 2024 Dec 26.
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.
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.
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.
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.
酒精使用障碍（AUD）的一个特征是尽管存在负面后果仍继续饮酒。本研究调查了选择性培育的嗜酒品系中的初始/早期抗厌恶饮酒（ARD）情况，以在乙醇接触史最少的情况下评估抗厌恶能力以及随后的乙醇寻求和饮酒模式。此外，使用蔗糖强化剂对嗜酒和不嗜酒大鼠的ARD进行评估，以确定ARD是否可能是AUD的遗传风险因素。
将雄性和雌性嗜酒大鼠在其饲养笼中每天给予四种浓度的奎宁（0.03、0.10、0.30和1.00 g/L，随机顺序）于乙醇溶液中，持续30分钟，共12天。然后在操作性条件反射箱中评估其寻求和饮酒行为。另外几组嗜酒和不嗜酒大鼠以相同的每日随机顺序给予相同浓度的奎宁掺杂蔗糖。
在乙醇中，所有嗜酒品系表现相似，在最低浓度时对奎宁具有抗性。在饲养笼中，高饮酒量（HAD）1大鼠饮用的乙醇量与嗜酒（P）大鼠相似，而在操作性任务中则更类似于HAD2大鼠。在蔗糖中，与基线相比，P和HAD2大鼠在低浓度奎宁时表现出抗厌恶能力。总体而言，不嗜酒品系均对奎宁掺杂蔗糖敏感。
本研究表明，当乙醇作为强化剂时，嗜酒品系表现出相似的ARD。关于动机性反应，P大鼠表现出如先前观察到的高寻求和高饮酒行为。在饲养笼中，HAD1大鼠的饮酒行为与P大鼠相似，表明不同条件（即自由饮用与操作性接触）会影响这些品系之间的饮酒行为。重要的是，在蔗糖强化剂条件下，嗜酒大鼠比不嗜酒品系更具抗厌恶能力，而不嗜酒品系对厌恶更为敏感，这表明其总体上表现出低水平强迫行为的倾向。
