Citric acid water as an alternative to food restriction to motivate task performance in mice during touchscreen testing.

Rodent behavioral testing paradigms in touchscreen operant chambers have successfully provided insight into the neural mechanisms underlying various cognitive domains in healthy and disease models. Touchscreen testing has previously required food restriction to sufficiently motivate rodents to complete behavioral tests, limiting the use of interventions, for example, diet-based interventions, that alter animals' motivation for food in experimental design. Here we explored the safety and efficacy of water manipulation via the addition of citric acid in motivating behavioral performance in touchscreen operant chambers (1) in comparison with food restriction and (2) when mice are fed an obesogenic high-fat, high-sugar (HFHS) diet. Water manipulation and food restriction produced similar performance on the progressive ratio task in nonobesogenic, standard-fed mice. However, when water-manipulated mice were fed an HFHS diet, they showed deficits in this motivation-sensitive task compared with standard chow-fed mice. Critically, all groups, regardless of restriction type or diet, showed similar learning curves during a pairwise visual discrimination task. Together, these findings demonstrate that water manipulation can safely and effectively motivate mice to perform touchscreen tasks for reward, even when fed a highly satiating HFHS diet, which opens the possibility of using interventions, especially diet-based interventions, in conjunction with touchscreen cognitive testing batteries.