Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation

Eur J Neurosci. 2008 Jun;27(11):2821-9. doi: 10.1111/j.1460-9568.2008.06266.x.


Daily life stressors are a major environmental factor contributing to precipitation and exacerbation of mental illness. Animal models using repeated homotypic stress induce anxious and depressive phenotypes and are used to study the pathophysiology of affective disorders. Here we discuss data demonstrating that repeated homotypic stress produces temporally and anatomically distinct changes in endocannabinoid signaling components within stress-responsive brain regions. We also present evidence describing the neural and behavioral correlates of these adaptations in endocannabinoid signaling. These data support a role for endocannabinoid signaling in the central nervous system response to chronic, homotypic stress, and specifically in the process of stress-response habituation. The clinical implications of these findings for the pathophysiology and treatment of affective disorders are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology*
  • Animals
  • Anxiety Disorders / etiology
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Brain / metabolism*
  • Brain / physiopathology
  • Cannabinoid Receptor Modulators / metabolism*
  • Depressive Disorder / etiology
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Endocannabinoids*
  • Humans
  • Mood Disorders / etiology
  • Mood Disorders / metabolism*
  • Mood Disorders / physiopathology
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology


  • Cannabinoid Receptor Modulators
  • Endocannabinoids