Journal article
Endogenous cannabinoid signaling is essential for stress adaptation
Proceedings of the National Academy of Sciences - PNAS, Vol.107(20), pp.9406-9411
05/18/2010
Handle:
https://hdl.handle.net/2376/105865
PMCID: PMC2889099
PMID: 20439721
Abstract
Secretion of glucocorticoid hormones during stress produces an array of physiological changes that are adaptive and beneficial in the short term. In the face of repeated stress exposure, however, habituation of the glucocorticoid response is essential as prolonged glucocorticoid secretion can produce deleterious effects on metabolic, immune, cardiovascular, and neurobiological function. Endocannabinoid signaling responds to and regulates the activity of the hypothalamic–pituitary–adrenal (HPA) axis that governs the secretion of glucocorticoids; however, the role this system plays in adaptation of the neuroendocrine response to repeated stress is not well characterized. Herein, we demonstrate a divergent regulation of the two endocannabinoid ligands,
N
-arachidonylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), following repeated stress such that AEA content is persistently decreased throughout the corticolimbic stress circuit, whereas 2-AG is exclusively elevated within the amygdala in a stress-dependent manner. Pharmacological studies demonstrate that this divergent regulation of AEA and 2-AG contribute to distinct forms of HPA axis habituation. Inhibition of AEA hydrolysis prevented the development of basal hypersecretion of corticosterone following repeated stress. In contrast, systemic or intra-amygdalar administration of a CB
1
receptor antagonist before the final stress exposure prevented the repeated stress-induced decline in corticosterone responses. The present findings demonstrate an important role for endocannabinoid signaling in the process of stress HPA habituation, and suggest that AEA and 2-AG modulate different components of the adrenocortical response to repeated stressor exposure.
Metrics
10 Record Views
Details
- Title
- Endogenous cannabinoid signaling is essential for stress adaptation
- Creators
- Matthew N Hill - Departments ofRyan J McLaughlin - Departments ofBrenda Bingham - Cellular and Physiological SciencesLalita Shrestha - Department of Pharmacology and ToxicologyTiffany T. Y Lee - Departments ofJ. Megan Gray - Cellular and Physiological SciencesCecilia J Hillard - Department of Pharmacology and ToxicologyBoris B Gorzalka - Departments ofVictor Viau - Cellular and Physiological Sciences
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.107(20), pp.9406-9411
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- National Academy of Sciences
- Identifiers
- 99900546950501842
- Language
- English
- Resource Type
- Journal article