Validation of a touchscreen probabilistic reward task for mice: A reverse-translated assay with cross-species continuity

The Probabilistic Reward Task (PRT) is a laboratory-based technique used to objectively quantify responsivity to reward. The PRT was initially designed to identify reinforcement learning deficits in clinical populations and subsequently was reverse-translated for use in preclinical studies with rats and monkeys. In this task, subjects make visual discriminations and asymmetric probabilistic contingencies are arranged such that correct responses to one stimulus (rich) are reinforced more often than correct responses to the other (lean). Numerous studies have demonstrated that healthy subjects reliably develop a response bias toward the richly rewarded stimulus, whereas humans with anhedonia and laboratory animals with a history of chronic stress exhibit a blunted response bias. This is important because anhedonia, the loss of responsivity to previously rewarding stimuli, is a behavioral phenotype that is a cardinal feature of multiple neuropsychiatric conditions and is without approved pharmacotherapeutic options. To aid in addressing this critical treatment gap, this report describes validation of the first PRT designed for mice, which are a commonly utilized species in preclinical research toward neuropsychiatric medications development. Results reveal orderly psychophysical functions in response to asymmetric probabilistic contingencies in mice, with signal detection outcomes comparable to previous PRT findings in humans, rats, and monkeys. Taken together, such robust cross-species continuity in task performance confirms that the mouse is well-positioned to serve in bidirectional research efforts between human and animal laboratories. These efforts may accelerate the development of treatment options for anhedonia in the different neuropsychiatric conditions in which it is prominent.