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.
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1469-5111
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Wellcome Trust (104631/Z/14/Z)
Medical Research Council (MC_G0802534)