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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: 2011-12, Psychopharmacology (Berl)., 218(3):589-97. Epub 2011 May 19.

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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