Cortical dopamine reduces the impact of motivational biases governing automated behaviour.
Autor: | Scholz V; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. vanessa.scholz@donders.ru.nl.; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre of Mental Health, University of Würzburg, Margarete-Höppel-Platz1, 97080, Würzburg, Germany. vanessa.scholz@donders.ru.nl., Hook RW; Department of Psychiatry, University of Cambridge, Cambridge, UK., Kandroodi MR; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.; School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran., Algermissen J; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Ioannidis K; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK.; Department of International Health, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands., Christmas D; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK., Valle S; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA., Robbins TW; Department of Psychology, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK., Grant JE; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA., Chamberlain SR; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Department of Psychiatry, Faculty of Medicine, University of Southampton, Southampton, UK. Southern Health NHS Foundation Trust, Southampton, UK., den Ouden HEM; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. hanneke.denouden@donders.ru.nl. |
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Jazyk: | angličtina |
Zdroj: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2022 Jul; Vol. 47 (8), pp. 1503-1512. Date of Electronic Publication: 2022 Mar 08. |
DOI: | 10.1038/s41386-022-01291-8 |
Abstrakt: | Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms. (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.) |
Databáze: | MEDLINE |
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