Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour

Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson's disease.

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Publication Details

Journal
Nature Communications
Published
2025-02-21
DOI
https://doi.org/10.1038/s41467-025-56663-7
Citations
13
Primary Topic
Neurotransmitter Receptor Influence on Behavior
Type
article
Field-Weighted Citation Impact
11.82

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article

Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour

Oliver Howes, Mitul A. Mehta, Robin M. Murray, Ben K. Statton et al.
13 citations
Nature Communications
Neurotransmitter Receptor Influence on Behavior
11.82
article

Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour

Oliver Howes, Mitul A. Mehta, Robin M. Murray, Ben K. Statton, Ellis Chika Onwordi, George E. Chapman, Thomas Whitehurst, Matthew B. Wall, Pierluigi Selvaggi, Tiago Reis Marques, Robert Ali McCutcheon, Uzma Zahid, Martin Osugo, Valeria Finelli
article en
13 citations

Abstract

Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson's disease.

Nature CommunicationsVol. 16(1)
Queen Mary University of London (GB), King's College London (GB), South London and Maudsley NHS Foundation Trust (GB), North East London NHS Foundation Trust (GB), East London NHS Foundation Trust (GB), Oxford Health NHS Foundation Trust (GB), University of Oxford (GB), Faculty (United Kingdom) (GB), Perceptive Engineering (United Kingdom) (GB), MRC London Institute of Medical Sciences (GB), University College London (GB), Imperial College London (GB), University of Bari Aldo Moro (IT)
South London and Maudsley NHS Foundation Trust, Wellcome Trust, Maudsley Charity, National Institute for Health and Care Research, Department of Health and Social Care, King's College London, European Commission, Medical Research Council, NIHR Imperial Biomedical Research Centre, NIHR Sheffield Biomedical Research Centre
Openalex Percentile: Top 1%
Neurotransmitter Receptor Influence on Behavior
11.82
DOIOpen Access PDFOpenAlex
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