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Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation
Open accessAbstract
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.
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“Recent preclinical evidence indicates that stress also mobilizes the endocannabinoid (eCB) system in both the brain and the periphery, and that the eCB system can modulate behavioral and endocrine responses to both acute and chronic stress (Hill et al, 2010;Patel and Hillard, 2008).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Patel and Hillard, 2008
In the citing paper
“Despite the abovementioned diversity in central and peripheral functions, recent studies in animals [9] and humans [10] point to a major role of EC signaling in both the periphery [10] and central nervous system [11] in controlling adaptive processes to aversive situations and regulating and limiting stress reactions.”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [9]
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Hill, M. N., McLaughlin, R. J., Bingham, B., Shrestha, L., Lee, T. T. Y., Gray, J. M., Hillard, C. J., Gorzalka, B. B., & Viau, V. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914661107 · Cited by 349
“A growing body of evidence suggests that endocannabinoid signaling also contributes to the process of stress habituation (8).”
BackgroundSelf-citationCampos, A. C., Ortega, Z., Palazuelos, J., Fogaça, M. V., Aguiar, D. C., Díaz-Alonso, J., Ortega-Gutiérrez, S., Vázquez-Villa, H., Moreira, F. A., Guzmán, M., et al. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001502 · Cited by 313
“An emerging paradigm from cannabinoid research is that the eCB system constitutes an allostatic signalling system that contributes to cellular plasticity responses in adaptation to stress-induced alterations (Patel and Hillard, 2008).”
BackgroundBest Practice & Research Clinical Endocrinology & Metabolism
Grieb, M. (2009) · Cited by 276
Metadata
- Authors
- Patel, S., & Hillard, C. J.
- Affiliations
- Vanderbilt University Medical Center (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Patel, Sachin
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2008-06
- Volume
- 27
- Issue
- 11
- Pages
- 2821-2829
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2593941
- OpenAlex
- W1981670902
- Cited by
- 162
- References
- 95
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 13 · 2014: 12 · 2013: 18 · 2012: 15
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (F30 DA15575, R01DA016967, F30DA015575, R21DA022439)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- endocannabinoid signaling, stress habituation, chronic stress, anxiety, depression, mood disorders
- MeSH terms
- Adaptation, Physiological, Animals, Anxiety Disorders, Brain, Depressive Disorder, Disease Models, Animal, Humans, Stress, Psychological, Mood Disorders, Cannabinoid Receptor Modulators, Endocannabinoids
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