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


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Article Info

DATE

2012-07-10

AUTHORS

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

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. More... »

PAGES

1125-1135

References to SciGraph publications

  • 2002-03-25. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum in NATURE NEUROSCIENCE
  • 2007-02-06. Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality in PSYCHOPHARMACOLOGY
  • 2011-08-17. Reversible Gating of Endocannabinoid Plasticity in the Amygdala by Chronic Stress: A Potential Role for Monoacylglycerol Lipase Inhibition in the Prevention of Stress-Induced Behavioral Adaptation in NEUROPSYCHOPHARMACOLOGY
  • 2002-08. The endogenous cannabinoid system controls extinction of aversive memories in NATURE
  • 2009-08-19. Neurocircuitry of Mood Disorders in NEUROPSYCHOPHARMACOLOGY
  • 2009-07-22. The Neurocircuitry of Fear, Stress, and Anxiety Disorders in NEUROPSYCHOPHARMACOLOGY
  • 2010-06-23. Genetic Deletion of Fatty Acid Amide Hydrolase Alters Emotional Behavior and Serotonergic Transmission in the Dorsal Raphe, Prefrontal Cortex, and Hippocampus in NEUROPSYCHOPHARMACOLOGY
  • 2009-08-26. Suppression of Amygdalar Endocannabinoid Signaling by Stress Contributes to Activation of the Hypothalamic-Pituitary-Adrenal Axis in NEUROPSYCHOPHARMACOLOGY
  • 2009-08-12. Repeated Homotypic Stress Elevates 2-Arachidonoylglycerol Levels and Enhances Short-Term Endocannabinoid Signaling at Inhibitory Synapses in Basolateral Amygdala in NEUROPSYCHOPHARMACOLOGY
  • 2005-05-13. Stress and the brain: from adaptation to disease in NATURE REVIEWS NEUROSCIENCE
  • 2009-03-04. Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats in PSYCHOPHARMACOLOGY
  • 2009-04-02. The neuro-symphony of stress in NATURE REVIEWS NEUROSCIENCE
  • 2009-02-10. SK2 potassium channel over-expression in basolateral amygdala reduces anxiety, stress-induced corticosterone and dendritic arborization in MOLECULAR PSYCHIATRY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/mp.2012.90

    DOI

    http://dx.doi.org/10.1038/mp.2012.90

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044689240

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22776900


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