Back to Search
Start Over
Glucocorticoid-endocannabinoid uncoupling mediates fear suppression deficits after early - Life stress
- Source :
- Psychoneuroendocrinology, 91, 41-49, Psychoneuroendocrinology, 91, pp. 41-49
- Publication Year :
- 2017
-
Abstract
- Contains fulltext : 193221.pdf (Publisher’s version ) (Closed access) Early-life stress (ELS) creates life-long vulnerability to stress-related anxiety disorders through altering stress and fear systems in the brain. The endocannabinoid system has emerged as an important regulator of the stress response through a crosstalk with the glucocorticoid system, yet whether it plays a role in the persistent effects of ELS remains unanswered. By combining, behavioral, pharmacological and biochemical approaches in adult male rats, we examined the impact of ELS on the regulation of endocannabinoid function by stress and glucocorticoids. We employed a postnatal limited-nesting/bedding induced ELS between postnatal days 2-9 in rats. Exposure to postnatal ELS compromised the ability of both acute stress and glucocorticoid administration to mobilize the endocannabinoid ligand 2-arachidonoyl glycerol (2-AG) in the hippocampus of adult male rats. These findings suggest that ELS compromises the coupling of the glucocorticoid and endocannabinoid systems in the hippocampus. Since 2-AG signaling is essential in mediating glucocorticoid-induced suppression of fear recall, we further examined the impact of ELS on the ability of glucocorticoids to suppress fear memory recall. While ELS did not affect normative fear recall, it impaired the ability of glucocorticoids to dampen fear recall. Notably, bypassing glucocorticoids and directly amplifying hippocampal 2-AG signaling with a monoacyl glycerol lipase inhibitor produced a suppression of fear memory recall in animals exposed to ELS. These findings suggest that ELS results in an uncoupling of glucocorticoid-endocannabinoid signaling in the hippocampus, which, in turn, relates to alterations in stress regulation of memory recall. These data provide compelling evidence that ELS-induced deficits in the glucocorticoid-endocannabinoid coupling following stress could predispose susceptibility to stress-related psychopathology.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13]
Early life stress
Regulator
Neurophysiology
Arachidonic Acids
Hippocampal formation
Anxiety
Hippocampus
Glycerides
Fight-or-flight response
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Endocrinology
Receptors, Glucocorticoid
Memory
Limbic System
Medicine
Animals
Glucocorticoids
Biological Psychiatry
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Early-life stress
Endocannabinoid
Fear recall
Glucocorticoid
Anxiety Disorders
Corticosterone
Endocannabinoids
Fear
Mental Recall
Rats
Stress, Psychological
Recall
Endocrine and Autonomic Systems
business.industry
Endocannabinoid system
Psychiatry and Mental health
030104 developmental biology
medicine.symptom
business
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 18733360 and 03064530
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Psychoneuroendocrinology
- Accession number :
- edsair.doi.dedup.....aecf82993ab3efb7839f919a096c8726