Investigating the Role of Central Endocannabinoids and Inflammation in Comorbid Anxiety-Like Behaviour and Colitis
AdvisorHill, Matthew Nicholas
AuthorVecchiarelli, Haley Alleson
Committee MemberSharkey, Keith A.
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AbstractThere is a well-established connection between inflammatory disorders and stress-associated neuropsychiatric disorders. For example, in patients with chronic inflammatory diseases, there are increased indices of anxiety and depression. However, despite this clinically significant relationship, there is not a comprehensive insight of the mechanisms linking inflammatory diseases with co-morbid mood and anxiety disorders. The endocannabinoid system, which is the system in the body that the psychoactive constituents of cannabis act on, regulates both anxiety and inflammation—indicating that it has the potential to underly these comorbidities. We hypothesize that in a rodent model of peripheral (gastrointestinal) inflammation, there would be alterations in endocannabinoid signaling that drive anxiety-like behaviours; that by boosting endocannabinoid signaling, these behaviours can be reversed; that neuroinflammation contributes to changes in central endocannabinoids.; and that endocannabinoids have the potential to regulate inflammatory processes. We find, using a rat model of colitis (intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS)), that there are reductions of an endocannabinoid, anandamide, in brain regions that regulate anxiety, which contributes to the generation of anxiety-like behaviour. We further show that these reductions are driven through corticotropin releasing factor receptor 1 (CRF-R1) and neuroinflammation mechanisms. Using a transgenic mouse model which presents elevated anandamide levels, we find a role for anandamide in regulating peripheral and central inflammatory changes induced by colitis. These studies link endocannabinoids and neuroinflammation to anxiety-like behaviour and show a protective role for endocannabinoid signaling in colitis-induced anxiety in rats and in peripheral and central inflammation in mice. This work contributes to our understanding of the mechanisms underlying inflammation induced anxiety.
CitationVecchiarelli, H. A. (2020). Investigating the Role of Central Endocannabinoids and Inflammation in Comorbid Anxiety-Like Behaviour and Colitis (Unpublished doctoral thesis). University of Calgary, Calgary, AB.
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