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Review
. 2011;13(4):463-74.
doi: 10.31887/DCNS.2011.13.4/mdavis.

NMDA receptors and fear extinction: implications for cognitive behavioral therapy

Michael Davis  1
Affiliations
Review

NMDA receptors and fear extinction: implications for cognitive behavioral therapy

Michael Davis. Dialogues Clin Neurosci. 2011.

Abstract
in English, Spanish, French

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.

Principaimente mediante esiudios que empiean el miedo condicionado pavloviano se ha encontrado que la extinción del miedo condicionado es mediada por receptores de N-metil-D-aspartato (NMDA) locaiizados en ia amígdala y en la corteza prefrontal medial. Esto llevó al descubrimiento que la D-cicloserina, un agonista parcial del NMDA, podría facilitar la extinción del miedo al administrarse en forma sistémica o localmente en la amígdala. Ya que muchas formas de terapia cognitivo conductual dependen de la extinción del miedo, se ha empleado con éxito la cicloserina como tratamiento conjunto con la psicoterapia en pacientes con fobias simples (temor a la altura), fobia social, conductas obsesivo-compulsivas y trastorno de pánico. Además se revisa la información que sustenta estas conclusiones y algunas de las posibles limitaciones de la D-cicloserina como tratamienio conjunto con la psicoterapia.

Selon des études qui emploient le conditionnement pavlovien à la peur, les récepteurs NMDA (N-méthyl-D-aspartate) de l'amygdale et du cortex préfrontal médian assurent la médiation de l'extinction de la peur conditionnée ; ces résultats ont conduit à la découverte qu'un agoniste partiel au NMDA, la D-cyclosérine, pouvait faciliter l'extinction de la peur après administration par voie générale ou locale dans l'amygdale. Puisque de nombreuses formes de thérapie cognitivo-comportementale dépendent de l'extinction de la peur, la D-cyclosérine a été utilisée avec succès comme aide à la psychothérapie chez des patients atteints de phobies dites simples (vertige), de phobie sociale, de comportement obsessionnel compulsif et de trouble panique. Des données en faveur de ces conclusions sont proposées ainsi que certaines limites éventuelles de la D-cyclosérine comme traitement d'appoint à la psychothérapie.

Keywords: D-cycloserine; amygdala; learning; memory; psychotherapy.

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Figures

Figure 1A.
Figure 1A.. Figure 1. Facilitation of exposure-based psychotherapy by D-cycloserine (DCS) in patients with fear of heights (A); social phobia (B); obsessive-compulsive disorder (C), or panic disorder (D).
Reproduced from ref 74: Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear Arch Gen Psychiatry. 2004:61:1136-1144. Copyright © American Medical Association 2004: ref 77: Hofmann SG, Meuret AE, Smits JA, et al. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry. 2006:63:298-304. Copyright © American Medical Association 2006: ref 79: Wilhelm S, Buhlmann U, Tolin DF, et al. Augmentation of behavior therapy with D-cycloserine for obsessive-compulsive disorder. Am J Psychiatry. 2008:165:335-341: quiz 409. Copyright © Hanover 2008: ref 80: Otto MW, Tolin DF, Simon NM.etal. Efficacy of dcycloserine for enhancing response to cognitive-behavior therapy for panic disorder. Biol Psychiatry. 2010:67:365-370. Copyright © Elsevier 2010
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