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

Journal

BIOLOGICAL PSYCHIATRY
Volume 78, Issue 5, Pages E15-E27

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2015.06.008

Keywords

Antidepressant; Cannabinoid; D-Cycloserine; Exposure; Extinction; Fear; Glucocorticoid; Hydrocortisone; Morphine; Opioid; Propranolol

Funding

  1. National Institutes of Health [T32-GM08605, 1F31MH097397, R01MH096764]
  2. Burroughs Wellcome Fund
  3. National Institutes of Health/National Center for Research Resources base grant [P51RR000165]

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Posttraumatic stress disorder 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. Preclinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory that 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 posttraumatic stress disorder that have been developed via a bench to bedside translational model.

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