Facilitation of Extinction of Conditioned Fear by D-Cycloserine: Implications for Psychotherapy
Abstract
Excessive fear and anxiety are characteristic of disorders such as post-traumatic stress disorder (PTSD) and phobias and are believed to reflect abnormalities in neural systems governing the development and reduction of conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposure to a feared stimulus in the absence of an aversive event leads to a gradual reduction in the fear response to that stimulus. Like conditioned fear learning, extinction is dependent on a particular protein (the N-methyl-D-aspartate or NMDA receptor) in a part of the brain called the amygdala. Blockade of this receptor blocks extinction and improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Because exposure-based psychotherapy for fear disorders in humans resembles extinction in several respects, we investigated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with findings from the animal laboratory, patients receiving D-cycloserine benefited more from exposure-based psychotherapy than did placebo-treated controls. Although very preliminary, these data provide initial support for the use of cognitive enhancers in psychotherapy and demonstrate that preclinical studies in rodents can have direct benefits to humans.
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Understanding key mechanisms of extinction has already improved the effectiveness of extinction-based treatment.
“I mentioned above the work on fear conditioning and how understanding key mechanisms of extinction has already improved the effectiveness of extinction-based treatment (Davis et al. 2005).”
From Mediators and Mechanisms of Change in Psychotherapy Research (2007) · cites this paper as Davis et al. 2005
Cites
The neuroanatomical and neurochemical basis of conditioned fear
Fendt, M., & Fanselow, M. S. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00016-0 · Cited by 1,092 · see citing works
Ressler, K. J., Rothbaum, B. O., Tannenbaum, L., Anderson, P., Graap, K., Zimand, E., Hodges, L., & Davis, M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.11.1136 · Cited by 1,063 · see citing works
Self-citationBehavioral and Neural Analysis of Extinction
Myers, K. M., & Davis, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)01064-4 · Cited by 918 · see citing works
Self-citationExtinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala
Falls, W., Miserendino, M., & Davis, M. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00854.1992 · Cited by 673 · see citing works
Self-citationNeuroimaging studies of amygdala function in anxiety disorders
RAUCH, S. L., SHIN, L. M., & WRIGHT, C. I. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07096.x · Cited by 463 · see citing works
Effects of D-cycloserine on extinction of conditioned freezing.
Ledgerwood, L., Richardson, R., & Cranney, J. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.2.341 · Cited by 388 · see citing works
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Mediators and Mechanisms of Change in Psychotherapy Research
Kazdin, A. E. (2007) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.3.022806.091432 · Cited by 2,504 · see citing works
Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective
Grupe, D. W., & Nitschke, J. B. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3524 · Cited by 2,007 · see citing works
A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy
Norberg, M. M., Krystal, J. H., & Tolin, D. F. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.012 · Cited by 510 · see citing works
A review of current evidence for the causal impact of attentional bias on fear and anxiety
Van Bockstaele, B., Verschuere, B., Tibboel, H., De Houwer, J., Crombez, G., & Koster, E. H. W. (2014) · Psychological Bulletin · doi:10.1037/a0034834 · Cited by 485 · see citing works
Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder
Otto, M. W., Tolin, D. F., Simon, N. M., Pearlson, G. D., Basden, S., Meunier, S. A., Hofmann, S. G., Eisenmenger, K., Krystal, J. H., & Pollack, M. H. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.036 · Cited by 251 · see citing works
Treating posttraumatic stress disorder in first responders: a systematic review
Haugen, P. T., Evces, M., & Weiss, D. S. (2012) · Clinical Psychology Review · doi:10.1016/j.cpr.2012.04.001 · Cited by 226 · see citing works
Kredlow, M. A., Unger, L. D., & Otto, M. W. (2016) · Psychological Bulletin · doi:10.1037/bul0000034 · Cited by 130 · see citing works
Otto, M. W., Basden, S. L., Leyro, T. M., McHugh, R. K., & Hofmann, S. G. (2007) · CNS Spectrums · doi:10.1017/s1092852900020526 · Cited by 53 · see citing works
Advances in psychotherapy for generalized anxiety disorder.
Garfinkle, E. J., & Behar, E. (2012) · Current Psychiatry Reports · doi:10.1007/s11920-012-0263-1 · Cited by 12 · see citing works
- Authors
- Davis, M., Myers, K. M., Ressler, K. J., & Rothbaum, B. O.
- Affiliations
- Emory University (US)
- Department of Psychiatry & Behavioral Sciences
- Corresponding author
- Davis, Michael
- Venue
- Current Directions in Psychological Science
- Publisher
- SAGE Publications
- Published
- 2005-08
- Volume
- 14
- Issue
- 4
- Pages
- 214-219
- ISSN
- 0963-7214 (ISSN-L)
- 1467-8721
- OpenAlex
- W2129612711
- Cited by
- 43
- References
- 6
- Citations by year
- 2025: 3 · 2023: 1 · 2018: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Directions in Psychological Science (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- D-cycloserine, fear extinction, fear conditioning, NMDA receptor, amygdala, post-traumatic stress disorder, phobia, nootropic drugs, anxiety disorders
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