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THC decreases energy expenditure in rats with activity-based anorexia

Lisa Eckel
Florida State University

Co-Authors: Savoya Joyner, Florida State University

Objective: Elevated peripheral markers of inflammation and impaired cannabinoid signaling have been reported in patients with anorexia nervosa (AN). Because the endocannabinoid system modulates immune function, food intake, and energy expenditure, all of which are dysregulated in AN, it represents an important therapeutic target. Despite this, few studies have examined whether cannabinoids can attenuate AN symptoms. Here, we examined whether Δ⁹-tetrahydrocannabinol (THC) attenuates hypophagia, hyperactivity, weight loss, and inflammation in a pre-clinical animal model of activity-based anorexia (ABA).

Methods: ABA was induced in female rats by combining food restriction (2h access to food/day) with free access to running wheels (RWs). Rats were removed from the paradigm after losing 22% of their baseline body weight or 7 days, whichever occurred first. Rats in the ABA-THC group received daily injections of vehicle (1 mL/kg, i.p.) until they had lost 10-12% of their baseline body weight (by day 3) and then received daily injections of THC (1 mg/kg, i.p.). Control rats received daily injections of vehicle. At the end of the study, rats were perfused and brain tissue was processed for Iba1 immunoreactivity to quantify microglial expression (a measure of central inflammation) in brain areas that control energy balance.

Results: ABA-induced weight loss was attenuated by THC treatment, with ABA-THC rats losing about 12% less weight than ABA-VEH rats. This reduction in weight loss in ABA-THC rats was mediated by a selective decrease in energy expenditure, with ABA-THC rats displaying a 50% decrease in RW activity relative to ABA-VEH rats (day 4-7 average: 4477 ± 766 vs. 9810 ± 594 revolutions, p < 0.05).  Preliminary findings suggest that THC attenuated the number of Iba-1 positive neurons in the arcuate nucleus of the hypothalamus.

Conclusion: Daily THC treatment was effective in attenuating weight loss in rats with ABA. Ongoing work will determine whether this action of THC is mediated, at least in part, by decreasing neuroinflammation in brain areas that regulate energy balance.