Abstract: 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.

Key words: Behavioral paradigm, Decision impulsivity, Mice, Reward, Skinner box