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  Differential modulation of reinforcement learning by D2 dopamine and NMDA glutamate receptor antagonism

Jocham, G., Klein, T. A., & Ullsperger, M. (2014). Differential modulation of reinforcement learning by D2 dopamine and NMDA glutamate receptor antagonism. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 34(39), 13151-13162. doi:10.1523/JNEUROSCI.0757-14.2014.

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Jocham, Gerhard1, 2, 3, Author
Klein, Tilmann A.4, 5, Author           
Ullsperger, Markus6, 7, Author           
1Faculty of Economics and Management, Otto-von-Guericke-University Magdeburg, Germany, ou_persistent22              
2Center for Behavioral Brain Sciences, Otto-von-Guericke-University Magdeburg, Germany, ou_persistent22              
3Max Planck Institute for Neurological Research, Cologne, Germany, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
5Clinic of Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
6Department of Neuropsychology, Otto-von-Guericke-University Magdeburg, Germany, ou_persistent22              
7Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands, ou_persistent22              


Free keywords: Dopamine; Glutamate; NMDA; Prediction error; Reinforcement learning; Striatum
 Abstract: The firing pattern of midbrain dopamine (DA) neurons is well known to reflect reward prediction errors (PEs), the difference between obtained and expected rewards. The PE is thought to be a crucial signal for instrumental learning, and interference with DA transmission impairs learning. Phasic increases of DA neuron firing during positive PEs are driven by activation of NMDA receptors, whereas phasic suppression of firing during negative PEs is likely mediated by inputs from the lateral habenula. We aimed to determine the contribution of DA D2-class and NMDA receptors to appetitively and aversively motivated reinforcement learning. Healthy human volunteers were scanned with functional magnetic resonance imaging while they performed an instrumental learning task under the influence of either the DA D2 receptor antagonist amisulpride (400 mg), the NMDA receptor antagonist memantine (20 mg), or placebo. Participants quickly learned to select (“approach”) rewarding and to reject (“avoid”) punishing options. Amisulpride impaired both approach and avoidance learning, while memantine mildly attenuated approach learning but had no effect on avoidance learning. These behavioral effects of the antagonists were paralleled by their modulation of striatal PEs. Amisulpride reduced both appetitive and aversive PEs, while memantine diminished appetitive, but not aversive PEs. These data suggest that striatal D2-class receptors contribute to both approach and avoidance learning by detecting both the phasic DA increases and decreases during appetitive and aversive PEs. NMDA receptors on the contrary appear to be required only for approach learning because phasic DA increases during positive PEs are NMDA dependent, whereas phasic decreases during negative PEs are not.


Language(s): eng - English
 Dates: 2014-08-182014-02-142014-08-192014-09-242014-09-24
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.0757-14.2014
PMID: 25253860
PMC: PMC4262707
 Degree: -



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Title: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 34 (39) Sequence Number: - Start / End Page: 13151 - 13162 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1