小鼠二选一赌博实验范式设计及验证

Design and validation of a mouse two-choice gambling experimental paradigm

目的设计和验证一种小鼠赌博实验范式,为精神疾病模型相关的决策冲动行为提供客观的评估手段。方法本研究使用C57/BL6J小鼠验证实验范式。实验范式分为六个阶段任务,并设定每个阶段的完成标准与评价指标。阶段一为限食阶段,控制小鼠体质量为初始值的85%;阶段二为装置适应阶段,小鼠只在操作箱内取食;阶段三为触屏取食阶段,分为三个任务(初始触屏任务、二选一触屏任务和单一选择触屏任务),训练小鼠触摸屏幕上的白色方块取食。阶段四为基础触屏任务,小鼠同样触摸白色方块取食,但增加了任务间的间隔时间且不设置不同的奖励和风险大小;阶段五为强制选择任务,强制小鼠触摸白色方块取食,学习不同方块代表的奖励和风险大小;阶段六为自由选择任务,小鼠自由选择高风险和低风险的方块获得不同大小的奖励,评价小鼠的决策冲动行为。结果各小鼠的装置适应阶段适应效果良好;触屏取食任务训练次数均大于130次/d;基础触屏任务正确率高于80.00%,错过率低于20.00%;强制选择任务的训练次数高于80次/d,正确率稳定在100.00%;自由选择任务训练次数高于60次/d,高风险选择比例在20.00%~30.00%。结论相较于其他范式,此范式训练后小鼠的准确率更高,避免了惩罚机制,提供了一种奖励依赖的决策冲动行为研究方法,对深入理解多种神经精神疾病的神经机制及其治疗方法的开发具有理论和应用价值。

Objective To design and validate a mouse gambling experimental paradigm so as to provide an objective measure to evaluate impulsivity in decision-making associated with neuropsychiatric diseases.Methods The experimental paradigm was validated using C57/BL6J mice.The experimental paradigm was structured into six sessions,each with specific criteria and assessment standards.The first session involved a food restriction phase,maintaining the mice's weight at 85%of the initial weight.The second session focused on apparatus adaptation,where mice obtained food solely within the operant chamber.The third session was dedicated to touchscreen training,subdivided into three tasks,i.e.,initial touchscreen task,two-choice touchscreen task,and single-choice touchscreen task,which trained mice to touch white squares on the screen to obtain food.The fourth session was the basic touchscreen task,in which the mice continued to touch white squares for food access,but intervals between tasks were introduced without varying the levels of reward or risk.The fifth session,the forced-choice task,required mice to touch white squares to get food,teaching them the associations among different squares and their corresponding rewards and risks.The sixth session introduced a free-choice task,allowing mice to freely choose between high-risk or low-risk squares for variable rewards,thereby evaluating their impulsivity in decision-making.Results The number of completed trials in the touchscreen tasks exceeded 130 times per day.In the basic touchscreen task,the accuracy rate was above 80.00%,with a missing rate below 20.00%.The number of completed trials in the forced-choice task exceeded 80 times per day,with a consistent accuracy rate of 100.00%.In the free-choice task,the number of completed trials exceeded 60 times per day,with high-risk proportions ranging from 20.00%to 30.00%.Conclusion This paradigm outperforms alternative models by yielding higher accuracy in trained mice and avoids the use of punitive measures,providing a reward-dependent approach to studying impulsivity in decision-making.It holds significant theoretical and practical value in advancing our understanding of the neural mechanisms underlying neuropsychiatric diseases and in the development of new treatment strategies.