title: Stress regulates endocannabinoid-CB1 receptor signaling.
abstract: The CB1 cannabinoid receptor is a G protein coupled receptor that is widely expressed throughout the brain. The endogenous ligands for the CB1 receptor (endocannabinoids) are N-arachidonylethanolamine and 2-arachidonoylglycerol; together the endocannabinoids and CB1R subserve activity dependent, retrograde inhibition of neurotransmitter release in the brain. Deficiency of CB1 receptor signaling is associated with anhedonia, anxiety, and persistence of negative memories. CB1 receptor-endocannabinoid signaling is activated by stress and functions to buffer or dampen the behavioral and endocrine effects of acute stress. Its role in regulation of neuronal responses is more complex. Chronic variable stress exposure reduces endocannabinoid-CB1 receptor signaling and it is hypothesized that the resultant deficiency in endocannabinoid signaling contributes to the negative consequences of chronic stress. On the other hand, repeated exposure to the same stress can sensitize CB1 receptor signaling, resulting in dampening of the stress response. Data are reviewed that support the hypothesis that CB1 receptor signaling is stress responsive and that maintaining robust endocannabinoid/CB1 receptor signaling provides resilience against the development of stress-related pathologies.
authors.affiliation: Neuroscience Research Center, Medical College of Wisconsin, United States; Department of Pharmacology and Toxicology, Medical College of Wisconsin, United States. Electronic address: chillard@mcw.edu.
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
mesh_terms: D000339:Affect / Q000502:physiology; D059445:Anhedonia; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D063388:Endocannabinoids / Q000378:metabolism*; D005786:Gene Expression Regulation; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018377:Neurotransmitter Agents; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate; C078814:anandamide
keywords: Cannabinoid; Endocannabinoid; Glucocorticoid; Stress