Knockout of the Serotonin Transporter in the Rat Mildly Modulates Decisional Anhedonia.

Serotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of serotonin transporter gene knockout (5-HTT-/-) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT-/- contributes to decisional anhedonia. To this end, we established a novel touchscreen-based go/go task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+ rats performed more optimal decision-making compared to 5-HTT-/- rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+ rats increased as the session increased in general, while 5-HTT-/- rats tended to decrease. The response time difference might indicate that 5-HTT-/- rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.

Knockout serotonin transporter in rats moderates outcome and stimulus generalization.

Understanding the common dimension of mental disorders (such as anxiety, depression, and drug addiction) might contribute to the construction of biological frameworks (Research Domain Criteria, RDoC) for novel ways of treatment. One common dimension at the behavioral level observed across these disorders is a generalization. Testing generalization in serotonin transporter (5-HTT) knockout (KO) rats, an animal model showing depression/anxiety-like behaviors and drug addiction-like behaviors, could therefore provide more insights into this framework. We tested the outcome and stimulus generalization in wild-type (WT) and 5-HTT KO rats. Using a newly established touchscreen-based task, subjects directly responded to visual stimuli (Gabor patch images). We measured the response time and outcome in a precise manner. We found that 5-HTT KO rats processed visual information faster than WT rats during outcome generalization. Interestingly, during stimulus generalization, WT rats gradually responded faster to the stimuli as the sessions progressed, while 5-HTT KO rats responded faster than WT in the initial sessions and did not change significantly as the sessions progressed. This observation suggests that KO rats, compared to WT rats, may be less able to update changes in information. Taken together, KO 5-HTT modulates information processing when the environment changes.