Endogenous cannabinoid signaling is essential for stress adaptation
Top Cited Papers
- 3 May 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (20), 9406-9411
- https://doi.org/10.1073/pnas.0914661107
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.Keywords
This publication has 40 references indexed in Scilit:
- Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoidsProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2009
- Basolateral amygdala efferents to the ventral subiculum preferentially innervate pyramidal cell dendritic spinesBrain Research, 2003
- Role of Endogenous Cannabinoids in Synaptic SignalingPhysiological Reviews, 2003
- Nongenomic Glucocorticoid Inhibition via Endocannabinoid Release in the Hypothalamus: A Fast Feedback MechanismJournal of Neuroscience, 2003
- Role of the Basolateral Amygdala in Memory ConsolidationAnnals of the New York Academy of Sciences, 2003
- Modulation of anxiety through blockade of anandamide hydrolysisNature Medicine, 2002
- A Cholecystokinin-Mediated Pathway to the Paraventricular Thalamus Is Recruited in Chronically Stressed Rats and Regulates Hypothalamic-Pituitary-Adrenal FunctionJournal of Neuroscience, 2000
- Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organizedJournal of Neuroscience, 1996
- Repeated stress persistently elevates morning, but not evening, plasma corticosterone levels in male ratsPhysiology & Behavior, 1994
- Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the ratNeuroscience, 1991