Year: 2025
Type: article
Study design: Clinical Trial
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.
Source: Nature Communications
Institutions: King's College London, South London and Maudsley NHS Foundation Trust, Imperial College London, University of Bari Aldo Moro, North London NHS Foundation Trust, University College London, East London NHS Foundation Trust, Queen Mary University of London, Oxford Health NHS Foundation Trust, University of Oxford
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: 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
Awards: G3447983802, G3620333518, G434337789, G5109539065, Neurobiological determinants of treatment response in psychosis., Neurobiological determinants of treatment response in psychosis., Using real-world big data from eHealth, biobanks and national registries, integrated with clinical trial data to improve outcome of severe mental disorders
OpenAlex ID: W4407840049