Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour
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-bl...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56663-7 |
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| author | Martin Osugo Matthew B. Wall Pierluigi Selvaggi Uzma Zahid Valeria Finelli George E. Chapman Thomas Whitehurst Ellis Chika Onwordi Ben Statton Robert A. McCutcheon Robin M. Murray Tiago Reis Marques Mitul A. Mehta Oliver D. Howes |
| author_facet | Martin Osugo Matthew B. Wall Pierluigi Selvaggi Uzma Zahid Valeria Finelli George E. Chapman Thomas Whitehurst Ellis Chika Onwordi Ben Statton Robert A. McCutcheon Robin M. Murray Tiago Reis Marques Mitul A. Mehta Oliver D. Howes |
| author_sort | Martin Osugo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cee44aaaa3344e798c69add858247bdc |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cee44aaaa3344e798c69add858247bdc2025-08-20T02:15:12ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-56663-7Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviourMartin Osugo0Matthew B. Wall1Pierluigi Selvaggi2Uzma Zahid3Valeria Finelli4George E. Chapman5Thomas Whitehurst6Ellis Chika Onwordi7Ben Statton8Robert A. McCutcheon9Robin M. Murray10Tiago Reis Marques11Mitul A. Mehta12Oliver D. Howes13Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonPerceptiveDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonMRC Laboratory of Medical Sciences, Imperial College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonMRC Laboratory of Medical Sciences, Imperial College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonAbstract 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.https://doi.org/10.1038/s41467-025-56663-7 |
| spellingShingle | Martin Osugo Matthew B. Wall Pierluigi Selvaggi Uzma Zahid Valeria Finelli George E. Chapman Thomas Whitehurst Ellis Chika Onwordi Ben Statton Robert A. McCutcheon Robin M. Murray Tiago Reis Marques Mitul A. Mehta Oliver D. Howes Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour Nature Communications |
| title | Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour |
| title_full | Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour |
| title_fullStr | Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour |
| title_full_unstemmed | Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour |
| title_short | Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour |
| title_sort | striatal dopamine d2 d3 receptor regulation of human reward processing and behaviour |
| url | https://doi.org/10.1038/s41467-025-56663-7 |
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