Addiction Neuroscience, Department of Psychology and Indiana Alcohol Research Center, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, United States.
Addiction Neuroscience, Department of Psychology and Indiana Alcohol Research Center, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, United States.
Alcohol. 2024 May;116:9-19. doi: 10.1016/j.alcohol.2023.10.001. Epub 2023 Oct 13.
Chronic alcohol consumption can lead to tolerance and escalation of drinking in humans and animals, but mechanisms underlying these changes are not fully characterized. Preclinical models can delineate which mechanisms are involved. The chronic intermittent ethanol exposure (CIE) procedure uses forced exposure to vaporized alcohol that elicits withdrawal and increased responding for alcohol in operant tasks in C57BL/6J inbred mice. Chronic two-bottle choice (2BC) drinking in the same strain elicits abstinent-related depression-like behavior, suggestive of allostatic changes. Selected lines such as crossed High Alcohol Preferring (cHAP) mice voluntarily drink to blood alcohol concentrations comparable to those attained in CIE and could be used to assess how alcohol affects these same endpoints without the confounds of involuntary vapor inhalation. In three experiments, we assess how 2BC drinking in cHAP mice affects abstinence-related depressive- and anxiety-like behavior, operant responding for alcohol, and binge consumption using drinking-in-the-dark (DID). We hypothesized that cHAPs with home-cage drinking experience would exhibit more depressive behavior after abstinence, increased responding for alcohol in the operant box, and increased DID intake. Of these, a drinking history increased DID intake in female cHAPs only and increased sucrose preference and intake following abstinence, but had no effects on operant responding or NSFT latency and FST immobility following forced abstinence. These results are consistent with recent findings using slice electrophysiology showing tolerance to alcohol's actions on the dorsolateral striatum following 2BC drinking in female, but not male cHAP mice. Overall, these data suggest that cHAPs may require procedures allowing rapid intoxication, such as DID, to demonstrate changes in alcohol's rewarding effects.
慢性酒精摄入可导致人类和动物的耐受和饮酒量增加，但这些变化的机制尚未完全阐明。临床前模型可以阐明涉及哪些机制。慢性间歇性乙醇暴露（CIE）程序使用强制暴露于蒸发的乙醇，在 C57BL/6J 近交系小鼠的操作性任务中引起戒断和对酒精的反应增加。在同一品系中进行慢性双瓶选择（2BC）饮酒会引起与禁欲相关的抑郁样行为，提示存在适应变化。像交叉高酒精偏好（cHAP）这样的选定品系自愿饮酒，血液酒精浓度可与 CIE 中达到的浓度相媲美，可用于评估酒精如何影响这些相同的终点，而不会受到非自愿吸入蒸气的干扰。在三个实验中，我们评估了 cHAP 小鼠的 2BC 饮酒如何影响与禁欲相关的抑郁和焦虑样行为、酒精的操作性反应以及狂欢性饮酒（DID）。我们假设，具有笼内饮酒史的 cHAP 会在禁欲后表现出更多的抑郁行为，在操作性箱中对酒精的反应增加，以及 DID 摄入量增加。其中，饮酒史仅增加了雌性 cHAP 的 DID 摄入量，并增加了禁欲后的蔗糖偏好和摄入量，但对操作性反应或强制禁欲后的 NSFT 潜伏期和 FST 不动性没有影响。这些结果与最近使用切片电生理学的研究结果一致，该研究表明，在雌性而非雄性 cHAP 小鼠中进行 2BC 饮酒后，对酒精对背外侧纹状体作用的耐受会增加。总的来说，这些数据表明，cHAP 可能需要允许快速醉酒的程序，例如 DID，才能显示酒精奖赏作用的变化。
