Quantitative Models of Reward Sensitivity to Examine Anhedonic Phenotypes in Rats
Authors: Kangas Brian D. , Luc Oanh T. , Wooldridge Lisa M. 
Published: April 2020

Anhedonia, the loss of pleasure derived from previously rewarding activities, is a behavioral phenotype that is implicated in several neuropsychiatric conditions, including major depressive disorder (MDD), schizophrenia, bipolar disorder, and drug dependence. Assessment of anhedonia in clinical populations has historically been derived from questionnaire metrics. However, these diagnostic instruments have shown poor reliability, especially in MDD, which has well‐documented high heterogeneity. The ubiquity of the anhedonic phenotype has led clinical researchers to develop quantitative assays to objectively characterize reward deficit profiles in the laboratory. One such approach is the Probabilistic Reward Task (PRT). Based on signal detection theory, the PRT uses visual discrimination methodology to quantify reward responsiveness across patient populations and healthy controls as a means to identify deficits. In the prototypical computerized task, human participants are required to make visual discriminations quickly across numerous trials. Unbeknownst to the participants, probabilistic contingencies are arranged such that correct responses to one alternative are rewarded more often (rich alternative) than correct responses on the other alternative (lean alternative). Healthy control participants consistently develop a response bias in favor of the rich alternative. Importantly, however, participants with MDD typically exhibit a lower response bias, relative to healthy controls, and this blunting of reward sensitivity has been documented to correlate with the severity of depressive symptoms. The present findings are from preclinical studies using human and rodent laboratory subjects to develop reverse translational (i.e., human‐to‐rat) assessments. Using recently developed customized touchscreen chambers for rats, we have developed a rodent PRT model variant that is formally and functionally similar to the human task described above. Rats were trained to discriminate between two white lines presented on the touchscreen that differed in length. Thereafter, probabilistic contingencies were introduced, biases were produced, and the effects of several drugs (e.g., amphetamine, scopolamine, and oxycodone) were examined for their ability to alter reward sensitivity. Results indicate reproducible probabilistic shifts in response biases that varied as a function of disparity in rich/lean arrangements and were similar in magnitude to those observed in humans. In addition, pharmacologically‐induced increases in bias via drugs known to enhance reward sensitivity (e.g., amphetamine, scopolamine) were observed in a dose‐dependent manner, thus verifying pharmacological sensitivity under this reverse‐translated rodent PRT. Taken together, the rodent PRT appears to have high preclinical value as a quantitative assay of reward responsiveness to examine the ability of drugs to alter hedonic tone.

Support or Funding Information

This research was supported by grant K01‐DA035974 from the National Institute on Drug Abuse.