Endocannabinoid signaling, glucocorticoid-mediated negative feedback, and regulation of the hypothalamic-pituitary-adrenal axis

Abstract The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of t...

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Bibliographic Details
Published in:Neuroscience 2012-03, Vol.204, p.5-16
Main Authors: Hill, M.N, Tasker, J.G
Format: Article
Language:English
Subjects:
2-AG
anandamide
Animals
cannabinoid
Cannabinoid Receptor Modulators - metabolism
CB1
Endocannabinoids
Feedback, Physiological - physiology
Glucocorticoids - metabolism
hpa axis
Humans
Hypothalamo-Hypophyseal System - metabolism
Neurology
Pituitary-Adrenal System - metabolism
Signal Transduction - physiology
stress
Stress, Psychological - metabolism
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Summary:Abstract The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of the stress response; however, the specific role endocannabinoid signaling plays in phases of HPA axis regulation, and the neural sites of action mediating this regulation, were not mapped out until recently. This review aims to collapse the current state of knowledge regarding the role of the endocannabinoid system in the regulation of the HPA axis to put together a working model of how and where endocannabinoids act within the brain to regulate outflow of the HPA axis. Specifically, we discuss the role of the endocannabinoid system in the regulation of the HPA axis under basal conditions, activation in response to acute stress, and glucocorticoid-mediated negative feedback. Interestingly, there appears to be some anatomical specificity to the role of the endocannabinoid system in each phase of HPA axis regulation, as well as distinct roles of both anandamide and 2-arachidonoylglycerol in these phases. Overall, the current level of information indicates that endocannabinoid signaling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala, and hypothalamus. This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2011.12.030