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THC attenuates weight loss in a preclinical animal model of activity-based anorexia

Savoya Joyner
Florida State University

Co-Authors: Lisa Eckel1
1Florida State University

Clinical studies report impaired cannabinoid signaling and elevated peripheral markers of inflammation in 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, there is a paucity of studies examining whether cannabinoids can attenuate AN symptoms. The current study examined whether Δ⁹-tetrahydrocannabinol (THC) attenuates hypophagia, hyperactivity, weight loss, and inflammation in a pre-clinical animal model of AN.

Female rats were exposed to the ABA paradigm, which combines food restriction (2h access to food/day) with unlimited access to running wheels (RWs). These conditions promote rapid, progressive weight loss, and rats are removed from the paradigm after losing 22% of their baseline body weight or 7 days, whichever occurs first. Rats in the ABA-VEH group received daily injections of vehicle (1 mL/kg, i.p.), whereas rats in the ABA-THC group received daily injections of vehicle for three days (at which time rats had lost 10-12% of their baseline body weight) followed by daily injections of THC on days 4-7 (1 mg/kg, i.p.). 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.

ABA-induced weight loss was attenuated by THC treatment, with ABA-THC rats losing less weight than ABA-VEH rats (33.9 ± 3.3 vs. 46.1 ± 3.8 g, p < 0.05). This effect of THC was mediated by a decrease in energy expenditure as ABA-THC rats displayed a 50% decrease in RW activity relative to ABA-VEH rats (day 4-7 average: 4477 ± 766 vs. 9810 ± 594 revolutions, p < 0.05). Food intake in ABA-THC and ABA-VEH groups was similar (day 4–7 average: 9.2 ± 0.6 vs. 10.0 ± 0.5 g).

Daily THC treatment helps to rescue the ABA phenotype in underweight, symptomatic female rats primarily through decreases in RW activity resulting in reduced energy expenditure. Ongoing analyses will determine whether microglial expression is elevated in ABA rats, and whether THC treatment attenuates ABA-induced inflammation.

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