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Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD

Academic Article
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Overview

authors

  • Andero, R.
  • Brothers, S. P.
  • Jovanovic, T.
  • Chen, Y. T.
  • Salah-Uddin, H.
  • Cameron, Michael
  • Bannister, Thomas
  • Almli, L.
  • Stevens, J. S.
  • Bradley, B.
  • Binder, E. B.
  • Wahlestedt, C.
  • Ressler, K. J.

publication date

  • June 2013

journal

  • Science Translational Medicine  Journal

abstract

  • The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.

subject areas

  • Adult
  • Amygdala
  • Animals
  • Anxiety
  • Conditioning (Psychology)
  • Cues
  • Disease Models, Animal
  • Fear
  • Female
  • Gene Expression Regulation
  • Humans
  • Immobilization
  • Male
  • Memory Disorders
  • Memory, Long-Term
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net
  • Piperidines
  • Receptors, Opioid
  • Stress Disorders, Post-Traumatic
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Identity

PubMed Central ID

  • PMC3732318

International Standard Serial Number (ISSN)

  • 1946-6234

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.3005656

PubMed ID

  • 23740899
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Additional Document Info

start page

  • 188ra73

volume

  • 5

issue

  • 188

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