Phillips, Benjamin U.; Dewan, Sigma; Nilsson, Simon R. O.; Robbins, Trevor W.; Heath, Christopher J.; Saksida, Lisa M.; Bussey, Timothy J. and Alsiö, Johan
(2018).
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| DOI (Digital Object Identifier) Link: | https://doi.org/10.1007/s00213-018-4907-7 |
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| Google Scholar: | Look up in Google Scholar |
Abstract
Rationale
Dysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress. Thus, we aimed to determine the impact of 5-HT2CR function on response to feedback in biased reinforcement learning.
Methods
We used two touchscreen assays designed to assess the impact of positive and negative feedback on probabilistic reinforcement in mice, including a novel valence-probe visual discrimination (VPVD) and a probabilistic reversal learning procedure (PRL). Systemic administration of a 5-HT2CR agonist and antagonist resulted in selective changes in the balance of feedback sensitivity bias on these tasks.
Results
Specifically, on VPVD, SB 242084, the 5-HT2CR antagonist, impaired acquisition of a discrimination dependent on appropriate integration of positive and negative feedback. On PRL, SB 242084 at 1 mg/kg resulted in changes in behaviour consistent with reduced sensitivity to positive feedback. In contrast, WAY 163909, the 5-HT2CR agonist, resulted in changes associated with increased sensitivity to positive feedback and decreased sensitivity to negative feedback.
Conclusions
These results suggest that 5-HT2CRs tightly regulate feedback sensitivity bias in mice with consequent effects on learning and cognitive flexibility and specify a framework for the influence of 5-HT2CRs on sensitivity to reinforcement.
| Item Type: | Journal Item |
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| Copyright Holders: | 2018 The Authors |
| ISSN: | 1432-2072 |
| Keywords: | 5-HT2C receptor; SB 242084; WAY 163909 |
| Academic Unit/School: | Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences Faculty of Science, Technology, Engineering and Mathematics (STEM) |
| Item ID: | 54422 |
| Depositing User: | Christopher Heath |
| Date Deposited: | 16 Apr 2018 13:47 |
| Last Modified: | 13 Aug 2019 10:50 |
| URI: | http://oro.open.ac.uk/id/eprint/54422 |
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