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Impaired learning from negative feedback in stimulant use disorder: Dopaminergic modulation

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Background: Drug-induced alterations to the dopamine system in stimulant use disorder (SUD) are hypothesised to impair reinforcement learning. Computational modelling enables the investigation of the latent processes of reinforcement learning in SUD patients, which could elucidate the nature of their impairments. Methods: We investigated reinforcement learning in 44 SUD patients and 41 healthy control participants using a probabilistic reinforcement learning task that assesses learning from reward and punishment separately. In an independent sample, we determined the modulatory role of dopamine in reinforcement learning following a single dose of the dopamine D2/3 receptor antagonist amisulpride (400 mg) and the agonist pramipexole (0.5 mg) in a randomised, double-blind, placebo-controlled, crossover design. We analysed task performance using computational modelling and hypothesised that reinforcement learning impairments in SUD patients would be differentially modulated by a dopamine D2/3 receptor antagonist and agonist. Results: Computational analyses in both samples revealed significantly reduced learning rates from punishment in SUD patients compared with healthy controls, whilst their reward learning rates were not measurably impaired. In addition, the dopaminergic receptor agents modulated reinforcement learning parameters differentially in both groups. Both amisulpride and pramipexole impaired reinforcement learning parameters in healthy participants, but ameliorated learning from punishment in SUD patients. Conclusion: Our findings suggest that reinforcement learning impairments seen in SUD patients are associated with altered dopamine function.



Addiction, cocaine, hierarchical Bayesian modeling, punishment, reinforcement learning, reward, Adult, Amphetamine-Related Disorders, Central Nervous System Stimulants, Cocaine-Related Disorders, Computer Simulation, Corpus Striatum, Cross-Over Studies, Dopamine, Dopamine Agonists, Dopamine Antagonists, Dopamine D2 Receptor Antagonists, Double-Blind Method, Feedback, Humans, Male, Pramipexole, Receptors, Dopamine D2, Receptors, Dopamine D3, Reinforcement, Psychology, Reward

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International Journal of Neuropsychopharmacology

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Cambridge University Press
Medical Research Council (MC_PC_17213)
Wellcome Trust (104631/Z/14/Z)
Medical Research Council (MC_G0802534)
This work was partly funded by GlaxoSmithKline (RG45422) and the NIHR Cambridge Biomedical Research Centre, and conducted within the Behavioural and Clinical Neuroscience Institute (BCNI). The views expressed are those of the authors and not the NIHR, the NHS or the Department of Health and Social Care. RNC’s research is funded by the UK Medical Research Council (MC_PC_17213). RNC consults for Campden Instruments Ltd and receives royalties from Cambridge University Press, Cambridge Enterprise, and Routledge. E.T.B. is an NIHR Senior Investigator; he serves on the Scientific Advisory Board of Sosei Heptares and as a consultant for GlaxoSmithKline. TWR discloses consultancy with Cambridge Cognition, Greenfield Bioventures, Heptares, Arcadia and Takeda; he is a recipient of Wellcome Trust Senior Investigator Award (104631/z/14/z), receives research grants from Shionogi and GlaxoSmithKline, royalties for the Cambridge Neuropsychological Test Automated Battery from Cambridge Cognition and editorial honoraria from Springer Verlag and Elsevier. KDE was supported by an Alexander von Humboldt Fellowship for senior researchers (GBR 1202805 HFST-E). The remaining authors declare no conflict of interest.