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Dialogues Clin Neurosci. 2011;13(4):463-74.

NMDA receptors and fear extinction: implications for cognitive behavioral therapy.

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Emory University, Yerkes National Primate Center and the Center for Behavioral Neuroscience, Atlanta, Georgia, USA.


Based primarily on studies that employ Pavlovian fear conditioning, extinction of conditioned fear has been found to be mediated by N-methyi-D-aspartate (NMDA) receptors in the amygdala and medial prefrontal cortex. This led to the discovery that an NMDA partial agonist, D-cycloserine, could facilitate fear extinction when given systemically or locally into the amygdala. Because many forms of cognitive behavioral therapy depend on fear extinction, this led to the successful use of D-cycloserine as an adjunct to psychotherapy in patients with so-called simple phobias (fear of heights), social phobia, obsessive-compulsive behavior, and panic disorder. Data in support of these conclusions are reviewed, along with some of the possible limitations of D-cycloserine as an adjunct to psychotherapy.


D-cycloserine; amygdala; learning; memory; psychotherapy

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