Functional interactions between stress and the endocannabinoid system: from synaptic signaling to behavioral output.
Endocannabinoid signaling is distributed throughout the brain, regulating synaptic release of both excitatory and inhibitory neurotransmitters. The presence of endocannabinoid signaling within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures such as the amygdala, suggests it may play an important role in regulating the neuroendocrine and behavioral effects of stress. The evidence reviewed here demonstrates that endocannabinoid signaling is involved in both activating and terminating the hypothalamic-pituitary-adrenal axis response to both acute and repeated stress. In addition to neuroendocrine function, however, endocannabinoid signaling is also recruited by stress and glucocorticoid hormones to modulate cognitive and emotional processes such as memory consolidation and extinction. Collectively, these data demonstrate the importance of endocannabinoid signaling at multiple levels as both a regulator and an effector of the stress response.
Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10065, USA. mhill@rockefeller.edu
Matthew N
MN
Hill
Sachin
S
Patel
Patrizia
P
Campolongo
Jeffrey G
JG
Tasker
Carsten T
CT
Wotjak
Jaideep S
JS
Bains
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005938:Glucocorticoids