Department of Psychology, Indiana Alcohol Research Center, Indiana University - Purdue University Indianapolis, Indianapolis, IN, USA.
Alcohol Clin Exp Res. 2021 Mar;45(3):650-660. doi: 10.1111/acer.14563. Epub 2021 Feb 17.
Current models of compulsive-like quinine-adulterated alcohol (QuA) drinking in mice, if improved, could be more useful for uncovering the neural mechanisms of compulsive-like alcohol drinking. The purpose of these experiments was to further characterize and improve the validity of a model of compulsive-like QuA drinking in C57BL/6J mice. We sought to determine whether compulsive-like alcohol drinking could be achieved following 2 or 3 weeks of Drinking-in-the-Dark (DID), whether it provides evidence for a robust model of compulsive-like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, whether repeated QuA exposures alter compulsive-like drinking, and whether there are sex differences in compulsive-like alcohol drinking.
Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for 2 hours each day for approximately 3 weeks. After 2 or 3 weeks, the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions on compulsive-like alcohol drinking was assessed. 3-minute front-loading, 2 hour binge-drinking, and blood alcohol concentrations were determined.
Compulsive-like QuA drinking was achieved after 3 weeks, but not 2 weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than nonadulterated alcohol at baseline. Thirty-minute front-loading of QuA revealed that alcohol history mice front-loaded significantly more QuA than water history mice, but still found the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive-like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge.
These data suggest that compulsive-like QuA drinking can be robustly achieved following 3 weeks of DID and male and female C57BL/6J mice do not differ in compulsive-like alcohol drinking.
目前用于小鼠强迫性类似奎宁加酒精（QuA）饮用量的模型，如果得到改进，可能更有助于揭示强迫性饮酒的神经机制。这些实验的目的是进一步描述和提高 C57BL/6J 小鼠强迫性类似 QuA 饮用量模型的有效性。我们试图确定以下情况是否可以实现强迫性类似酒精饮用量：2 或 3 周的暗饮（DID）后，通过包括水对照组和使用高浓度 QuA 溶液来提供强迫性类似酒精饮用量的有力模型的证据，重复 QuA 暴露是否会改变强迫性饮酒，以及在强迫性饮酒方面是否存在性别差异。
雄性和雌性 C57BL/6J 小鼠每天自由饮用 20%酒精或自来水 2 小时，持续约 3 周。2 或 3 周后，给予 QuA（500 μM），并评估重复 QuA 饮酒对强迫性类似酒精饮用量的影响。测定 3 分钟的前置负荷、2 小时的 binge 饮酒和血液酒精浓度。
3 周而不是 2 周的每日酒精接触可实现强迫性类似 QuA 饮用量，这是通过酒精史小鼠比水史小鼠消耗的 QuA 明显更多，并且在基线时与未掺杂酒精相比饮用的 QuA 量无统计学差异来确定的。QuA 的 30 分钟前置负荷表明，酒精史小鼠的 QuA 前置负荷明显多于水史小鼠，但仍发现 QuA 溶液令人厌恶。重复 QuA 暴露并未改变这些模式，强迫性饮酒没有性别差异，QuA 饮酒的 BAC 处于 binge 水平。
这些数据表明，3 周的 DID 后可以强有力地实现强迫性类似 QuA 饮用量，并且 C57BL/6J 雄性和雌性小鼠在强迫性饮酒方面没有差异。
