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N-Methyl D-aspartate receptor subunit signaling in fear extinction

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Abstract

N-Methyl D-aspartate receptors (NMDAR) are central mediators of glutamate actions underlying learning and memory processes including those required for extinction of fear and fear-related behaviors. Consistent with this view, in animal models, antagonists of NMDAR typically impair fear extinction, whereas partial agonists have facilitating effects. Promoting NMDAR function has thus been recognized as a promising strategy towards reduction of fear symptoms in patients suffering from anxiety disorders and post-traumatic disorder (PTSD). Nevertheless, application of these drugs in clinical trials has proved of limited utility. Here we summarize recent advances in our knowledge of NMDAR pharmacology relevant for fear extinction, focusing on molecular, cellular, and circuit aspects of NMDAR function as they relate to fear extinction at the level of behavior and cognition. We also discuss how these advances from animal models might help to understand and overcome the limitations of existing approaches in human anxiety disorders and how novel, more specific, and personalized approaches might help advance future therapeutic strategies.

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Funding

The authors acknowledge that this work was supported by NIH grants MH108837 and MH078064 to J.R. and by the National Natural Science Foundation of China grant 81471101 to C.G.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Jelena Radulovic & Lynn Y. Ren

  2. Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China

    Can Gao

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  1. Jelena Radulovic
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  2. Lynn Y. Ren
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  3. Can Gao
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Correspondence to Jelena Radulovic.

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This article belongs to a Special Issue on Psychopharmacology of Extinction

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Radulovic, J., Ren, L.Y. & Gao, C. N-Methyl D-aspartate receptor subunit signaling in fear extinction. Psychopharmacology 236, 239–250 (2019). https://doi.org/10.1007/s00213-018-5022-5

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  • DOI: https://doi.org/10.1007/s00213-018-5022-5

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