From the, Addiction Neuroscience (CEA, NJG, CCL), Department of Psychology, Indiana Alcohol Research Center, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.
Stark Neuroscience Institute (CCL), Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res. 2020 Sep;44(9):1717-1727. doi: 10.1111/acer.14419. Epub 2020 Aug 31.
Beyond yielding high blood ethanol (EtOH) concentrations (BECs), binge-drinking models allow examination of drinking patterns which may be associated with EtOH's rewarding effects, including front-loading and consummatory successive negative contrast (cSNC), a decrease in intake when only water is available to subjects expecting EtOH. The goals of the current study were to broaden our understanding of these reward-related behaviors during binge EtOH access in high alcohol-preferring (HAP) replicate lines (HAP2 and HAP3) of mice selectively bred to prefer alcohol. We hypothesized that both lines would show evidence of front-loading during binge EtOH access and that we would find a cSNC effect in groups where EtOH was replaced with water, as these results have been shown previously in HAP1 mice.
HAP replicate 2 and replicate 3 female and male mice were given 2 hours of EtOH or water access in the home cage for 15 consecutive days using "drinking in the dark" (DID) procedures. Mice received the same fluid (either 20% unsweetened EtOH or water) for the first 14 days. However, on the 15th day, half of the mice from these 2 groups were provided with the opposite assigned fluid (EtOH groups received water and vice versa). Intake was measured in 1-minute bins using specialized sipper tubes, which allowed within-session analyses of binge-drinking patterns.
EtOH front-loading was observed in both replicates. HAP3 mice displayed front-loading on the first day of EtOH access, whereas front-loading developed following alcohol experience in HAP2 mice, which may suggest differences in initial sensitivity to EtOH reward. Consummatory SNC, which manifests as lower water intake in mice expecting EtOH as compared to mice expecting water, was observed in both replicates.
These findings increase confidence that defined changes in home cage consummatory behavior are driven by the incentive value of EtOH. The presence of cSNC across HAP replicates indicates that this reaction to loss of reward is genetically mediated, which suggests that there is a biological mechanism that might be targeted.
除了产生高血液乙醇（EtOH）浓度（BEC）外， binge-drinking 模型还允许检查与 EtOH 的奖励作用相关的饮酒模式，包括前端加载和消耗性连续负对比（cSNC），当仅向预期 EtOH 的受试者提供水时，摄入量会减少。本研究的目的是扩大我们对这些在高酒精偏好（HAP）复制线（HAP2 和 HAP3）小鼠 binge EtOH 摄入期间与奖励相关的行为的理解，这些小鼠是通过选择性繁殖来偏好酒精的。我们假设这两条线在 binge EtOH 摄入期间都会显示前端加载的证据，并且我们会在用 EtOH 替代水的组中发现 cSNC 效应，因为这些结果之前在 HAP1 小鼠中已经显示过。
使用“暗饮”（DID）程序，在连续 15 天内，将 HAP 复制 2 和复制 3 的雌性和雄性小鼠在家笼中给予 2 小时的 EtOH 或水摄入。小鼠在前 14 天内接受相同的液体（20%未加糖的 EtOH 或水）。然而，在第 15 天，这两组中的一半小鼠接受了相反分配的液体（EtOH 组接受水，反之亦然）。使用专门的吮吸管以 1 分钟的间隔测量摄入量，这允许在单次饮酒期间分析 binge-drinking 模式。
在两种复制中都观察到 EtOH 的前端加载。HAP3 小鼠在 EtOH 摄入的第一天显示前端加载，而 HAP2 小鼠在酒精体验后发展出前端加载，这可能表明对 EtOH 奖励的初始敏感性不同。在两种复制中都观察到消耗性 SNC，其表现为与预期 EtOH 的小鼠相比，预期水的小鼠的水摄入量较低。
这些发现增加了对在家庭笼中消耗性行为的定义变化是由 EtOH 的激励价值驱动的信心。在 HAP 复制中存在 cSNC 表明这种对奖励损失的反应是由遗传介导的，这表明存在可能被靶向的生物学机制。
