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Author Notes:

Corresponding author at: Department of Pharmacology & Toxicology, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck Innrain 80-82, A-6020 Innsbruck, Austria. Fax: +43 512 507 58889. nicolas.singewald@uibk.ac.at (N. Singewald)

N. Singewald and C. Schmuckermair contributed equally to this work.

Drs. Singewald, Schmuckermair, Whittle and Holmes declare no conflict of interest.

Dr. Ressler is a founding member of Extinction Pharmaceuticals/Therapade Technologies.

He has received no equity or income from this relationship within the last 5 years.

The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies.

Subjects:

Research Funding:

We acknowledge the Austrian Science Fund [FWF grant numbers SFB F4410 and P25375-B24] for funding our research related to this review (NS).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Pharmacology & Pharmacy
  • Fear extinction
  • Exposure therapy
  • Augmented relearning
  • Reconsolidation
  • Drug development
  • Cognitive enhancer
  • POSTTRAUMATIC-STRESS-DISORDER
  • OBSESSIVE-COMPULSIVE DISORDER
  • FIBROBLAST-GROWTH-FACTOR
  • MEDIAL PREFRONTAL CORTEX
  • RANDOMIZED CONTROLLED-TRIAL
  • D-CYCLOSERINE AUGMENTATION
  • ACTIVATED PROTEIN-KINASE
  • PLACEBO-CONTROLLED TRIAL
  • RECEPTOR MESSENGER-RNA
  • GATED CALCIUM-CHANNELS

Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

Tools:

Journal Title:

Pharmacology and Therapeutics

Volume:

Volume 149

Publisher:

, Pages 150-190

Type of Work:

Article | Final Publisher PDF

Abstract:

Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example d-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.

Copyright information:

© 2014 The Authors. Published by Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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