Role of dopamine D2 receptors in human reinforcement learning.
Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.
1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
Christoph
C
Eisenegger
Department of Economics, Royal Holloway, University of London, Egham, UK.
Michael
M
Naef
Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands.
Anke
A
Linssen
1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Psychology, University of Cambridge, Cambridge, UK.
Luke
L
Clark
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Praveen K
PK
Gandamaneni
1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Cambridgeshire & Peterborough NHS Foundation Trust, Adult ADHD Service, Cambridge, UK.
Ulrich
U
Müller
1] Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, UK [2] Department of Psychology, University of Cambridge, Cambridge, UK.
Trevor W
TW
Robbins
D000328:Adult; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000097:blood / Q000494:pharmacology; D004311:Double-Blind Method; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008960:Models, Psychological; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012054:Reinforcement, Psychology; D013469:Sulpiride / Q000097:blood / Q000494:pharmacology; D055815:Young Adult
C581293:DRD2 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D011388:Prolactin