Valproic acid but not d-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans

Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takashi; Kim, Yoshiharu

doi:10.1016/j.neuropharm.2012.07.045

Cited by 28 publications

(21 citation statements)

References 56 publications

(58 reference statements)

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“…In healthy human volunteers, DCS facilitates consolidation of fear acquisition of previously neutral cues and cued fear extinction (60, 61). Other studies, have also not observe a reduction in conditioned fear with administration of DCS (62–64). For individuals with PTSD, DCS seems particularly effective when administered with virtual reality exposure (VRE) (65, 66).…”

Section: Pharmacotherapy Approaches To Fear- and Anxiety-related Disomentioning

confidence: 80%

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

Bowers

Ressler

2015

Biological Psychiatry

126

101

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Posttraumatic stress disorder (PTSD) manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Pre-clinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory, which have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for PTSD that have been developed via a bench to bedside translational model.

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Section: Pharmacotherapy Approaches To Fear- and Anxiety-related Disomentioning

confidence: 80%

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

Bowers

Ressler

2015

Biological Psychiatry

126

101

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“…These promising preclinical studies were translated across a number of exposure therapy paradigms in humans with clinical anxiety disorders (9,10,11,12,13). Despite these promising findings, studies examining fear extinction in healthy humans using skin conductance response found no D-cycloserine enhancement of extinction training or recall (32,33). However, similar to the rodent studies, D-cycloserine was found to significantly reduce reinstatement of fear after extinction (33) demonstrating potential long-term benefits of extinction learning.…”

Section: Discussionmentioning

confidence: 98%

A Randomized, Double-Blind Evaluation of d-Cycloserine or Alprazolam Combined With Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder in Iraq and Afghanistan War Veterans

Rothbaum¹,

Price²,

Jovanović³

et al. 2014

AJP

382

293

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Objective To determine the effectiveness of Virtual Reality Exposure (VRE) augmented with D-cycloserine (50mg) or alprazolam (0.25mg), compared to placebo, in reducing PTSD due to military trauma in Iraq and Afghanistan. Method A double-blind, placebo-controlled randomized clinical trial comparing augmentation methods for VRE for subjects (n= 156) with PTSD was conducted. Results PTSD symptoms significantly improved from pre- to post-treatment over the 6-session VRE treatment (p<.001) across all conditions and were maintained at 3, 6, and 12 months follow-up. There were no overall differences between the D-cycloserine group on symptoms at any time-point. The alprazolam and placebo conditions significantly differed on the post-treatment Clinician Administered PTSD scale (p = .006) and the 3-month post-treatment PTSD diagnosis, such that the alprazolam group showed greater rates of PTSD (79.2% alprazolam vs. 47.8% placebo). Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only (p<.005). At post-treatment, the D-cycloserine group was the lowest on cortisol reactivity (p<.05) and startle response during VR scenes (p<.05). Conclusions A small number of VRE sessions were associated with reduced PTSD diagnosis and symptoms in Iraq/Afghanistan veterans, although there was no control condition for the VRE. Overall, there was no advantage of D-cycloserine on PTSD symptoms in primary analyses. In secondary analyses, benzodiazepine use during treatment may impair recovery, and D-cycloserine may enhance VRE in patients who demonstrate within-session learning. D-cycloserine augmentation treatment in PTSD patients may reduce cortisol and startle reactivity compared to the alprazolam and placebo treatment, consistent with the animal literature.

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“…These have included targeting glucocorticoid (e.g. De Bitencourt et al, 2013), glutamtergic (Kuriyama et al, 2013), GABAergic (Rodríguez et al, 2013) adrenergic (Kindt et al, 2009), cannabinoid (Rabinak et al, 2013), serotonergic (Zhang et al, 2013) and glycine (File et al, 1999) receptors.…”

Section: If Only I Could Forget…mentioning

confidence: 99%

Enhance, delete, incept: Manipulating hippocampus-dependent memories

Spiers

Bendor

2014

Brain Research Bulletin

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Valproic acid but not d-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans

Cited by 28 publications

References 56 publications

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

A Randomized, Double-Blind Evaluation of d-Cycloserine or Alprazolam Combined With Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder in Iraq and Afghanistan War Veterans

Enhance, delete, incept: Manipulating hippocampus-dependent memories

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