title: A role beyond learning for NMDA receptors in reward-based decision-making-a pharmacological study using d-cycloserine.
abstract: N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA's roles in neuronal super-additivity and as crucial for evidence integration for decisions.
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scholl
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Günthner
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, UK.
authors.forename: Nils
authors.initials: N
authors.lastname: Kolling
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Elisa
authors.initials: E
authors.lastname: Favaron
authors.affiliation: 1] Department of Experimental Psychology, University of Oxford, Oxford, UK [2] Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), University of Oxford, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Matthew Fs
authors.initials: MF
authors.lastname: Rushworth
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Reinecke
mesh_terms: D000293:Adolescent; D000328:Adult; D000963:Antimetabolites / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D003657:Decision Making / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D012201:Reward; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000963:Antimetabolites; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine