Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Hill, M. N.
  • Kumar, S. A.
  • Filipski, S. B.
  • Iverson, M.
  • Stuhr, K. L.
  • Keith, J. M.
  • Cravatt, Benjamin
  • Hillard, C. J.
  • Chattarji, S.
  • McEwen, B. S.

publication date

  • October 2013

journal

  • Molecular Psychiatry  Journal

abstract

  • Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid (eCB) system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress, which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the eCB N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress.

subject areas

  • Amidohydrolases
  • Amygdala
  • Animals
  • Anxiety
  • Chronic Disease
  • Cyclohexanols
  • Dendrites
  • Drug Evaluation, Preclinical
  • Endocannabinoids
  • Exploratory Behavior
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyramidal Cells
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1
  • Restraint, Physical
  • Stress, Psychological
scroll to property group menus

Research

keywords

  • FAAH
  • anandamide
  • anxiety
  • basolateral amygdala
  • cannabinoid
  • stress
scroll to property group menus

Identity

PubMed Central ID

  • PMC4148304

International Standard Serial Number (ISSN)

  • 1359-4184

Digital Object Identifier (DOI)

  • 10.1038/mp.2012.90

PubMed ID

  • 22776900
scroll to property group menus

Additional Document Info

start page

  • 1125

end page

  • 1135

volume

  • 18

issue

  • 10

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support