Facilitation of Extinction of Conditioned Fear byD-Cycloserine
Implications for Psychotherapy
Karyn M. Myers,
Kerry J. Ressler,
Barbara O. Rothbaum
Psychiatry & Behavioral Sciences,
Center for Behavioral Neuroscience, and
Yerkes National Primate Research Center, Emory University
Excessive fear and anxiety are characteristicofdisorderssuchaspost-traumaticstressdisorder(PTSD)and phobias and are believed to reﬂect abnormalities inneural systems governing the development and reductionof conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposuretoafearedstimulusintheabsence ofanaversiveevent leads to a gradual reduction in the fear response tothat stimulus. Like conditioned fear learning, extinctionis 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 extinctionand improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Becauseexposure-based psychotherapy for fear disorders in hu-mans resembles extinction in several respects, we investi- gated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with ﬁndings from theanimal laboratory, patients receiving D-cycloserine bene- ﬁted more from exposure-based psychotherapy than did placebo-treatedcontrols.Althoughverypreliminary,thesedata provide initial support for the use of cognitive en-hancers in psychotherapy and demonstrate that preclini-cal studies in rodents can have direct beneﬁts to humans.
amygdala; exposure therapy; fear; NMDA; post-traumatic stress disorder; phobias; extinction
I can’t get the memories out of my mind! The images come ﬂooding back in vivid detail, triggered by the most inconsequen-tial things, like a door slamming or the smell of stir-fried pork. Last night, I went to bed, was having a good sleep for a change.Thenintheearlymorningastorm frontpassedthroughandthere wasaboltofcrackling thunder.Iawokeinstantly,frozen infear.I amrightback inVietnam, inthemiddleofthemonsoonseason atmy guard post. I am sure I’ll get hit in the next volley and con- vinced I will die. My hands are freezing, yet sweat pours from myentire body. I feel each hair on the back of my neck standing onend. I can’t catch my breath and my heart is pounding. I smell adampsulfursmell.SuddenlyIseewhat’sleftofmybuddyTroy,hisheadonabambooplatter,sentbacktoourcampbytheVietCong. Propagandamessagesarestuffed between his clenched teeth.Thenextboltoflightningandclapofthundermakesmejumpsomuchthat I fall to the ﬂoor
Perhaps there are no more vivid memories than those storedin the brains of soldiers who have experienced combat situa-tions. Witness the above account told by a 60-year-old Vietnamveteran who cannot hear a clapof thunder,see an Asian woman,or touch a bamboo placemat without re-experiencing the sightof his decapitated friend. Even though this traumatic eventoccurred in a faraway place and long ago, the memoryis still vivid in every detail and continues to produce the samestate of hyperarousal and fear as he experienced on that fatefulday.Once called combat fatigue, war neurosis, or shell shock, it isnowclearthatpost-traumaticstressdisorder(PTSD)resultsfromintensetraumaandproducesvividmemoriesthatlastalifetime.
Address correspondence to Michael Davis, Yerkes National PrimateResearch Center, Emory University, 954 Gatewood Rd NE, Atlanta,GA 30329; e-mail: firstname.lastname@example.org.
Paraphrased from a war veteran’s conversations with R.L. Gelman, Depart-ment of Psychiatry, Yale University School of Medicine (personal communica-tion).
CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE
Volume 14—Number 4Copyright
2005 American Psychological Society