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Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence

Alsiö, Johan; Phillips, Benjamin U.; Sala-Bayo, Júlia; Nilsson, Simon R. O.; Calafat-Pla, Teresa C.; Rizwand, Arazo; Plumbridge, Jessica M.; Lopez-Cruz, Laura; Dalley, Jeffrey W.; Cardinal, Rudolf N.; Mar, Adam C. and Robbins, Trevor W. (2019). Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence. Psychopharmacology, 236(8) pp. 2307–2323.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1007/s00213-019-05296-y
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Abstract

Rationale
Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson's disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.
Objectives
We tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.
Methods
Male Lister Hooded rats were trained on a novel visual reversal learning task. Performance on "probe trials", during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback. The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism. Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors.
Results
D2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials.
Conclusion
D2R stimulation impairs reversal learning by blocking the impact of negative feedback.

Item Type: Journal Item
Copyright Holders: 2019 The Authors
ISSN: 0033-3158
Keywords: Dopamine; Cognition; Dopamine D2 receptor; Rat; Dopamine D1 receptor; Reversal learning; Cognitive flexibility . Computational modelling . Hierarchical Bayesian analysis . Reinforcement learning
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: 66577
Depositing User: Laura Lopez-Cruz
Date Deposited: 26 Sep 2019 12:08
Last Modified: 29 Sep 2019 09:18
URI: http://oro.open.ac.uk/id/eprint/66577
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