Effect of D-cycloserine and valproic acid on the extinction of reinstated
fear-conditioned responses and habituation of fear conditioning in healthy
humans: a randomized controlled trial.
Author(s): Kuriyama K, Honma M, Soshi T, Fujii T, Kim Y.
Affiliation(s): Department of Adult Mental Health, National Institute of Mental Health, National
Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502,
Japan. kenichik@ncnp.go.jp
Publication date & source: 2011, Psychopharmacology (Berl). , 218(3):589-97
RATIONALE: Although the effects of D: -cycloserine (DCS) and valproic acid (VPA)
on the facilitation of the extinction of fear-conditioned memory have been
elucidated in animals, these effects have not been clearly confirmed in humans.
OBJECTIVE: This study aimed to determine the effect of DCS (100 mg) and VPA (400
mg) on the facilitation of the extinction and acquisition of fear-conditioned
memory in humans.
METHODS: We performed a randomized, blind, placebo-controlled, four-arm clinical
trial in 60 healthy adults. Visual cues and electric shocks were used as the
conditioned stimulus (CS) and unconditioned stimulus (US), respectively.
RESULTS: The extinction or acquisition effect was not observed in the simple
recall after the extinction or acquisition of coupled CS-US; however, the
extinction and habituation effects but not the acquisition effects were presented
after the unexpected re-exposure of coupled CS-US (reinstatement stimuli).
Extinction and habituation effects were facilitated by either a single dose of
DCS or VPA or a combination of DCS and VPA. However, we did not observe the
expected synergistic effect of the combined treatment on the extinction or
habituation of fear conditioning.
CONCLUSION: A single dose of DCS or VPA might enhance exposure-based cognitive
therapy of anxiety disorders by reducing the vulnerability to reinstatement and
preventing relapses of fear-conditioned responses.
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