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

多巴胺 D2 样受体刺激阻断大鼠视觉和空间逆转学习中的负反馈:行为和计算证据

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作者:Johan Alsiö, Benjamin U Phillips, Júlia Sala-Bayo, Simon R O Nilsson, Teresa C Calafat-Pla, Arazo Rizwand, Jessica M Plumbridge, Laura López-Cruz, Jeffrey W Dalley, Rudolf N Cardinal, Adam C Mar, Trevor W Robbins

Conclusions

D2R stimulation impairs reversal learning by blocking the impact of negative 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. Conclusions: D2R stimulation impairs reversal learning by blocking the impact of negative feedback.

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