Anorexia nervosa (AN) is characterized by
anhedonia whereby patients experience little pleasure or reward in many aspects of their lives. Reward pathways and the endocannabionid system have been implicated in the mediation of food intake. The potential to exploit these systems to reverse
weight loss is investigated in a rodent model of activity-based
anorexia (ABA). The effect of subchronic (6 days) Δ(9)-tetrahydrocannabinol (
THC) treatment (0.1, 0.5, or 2.0 mg/kg/day) was assessed on chow and high-fat diet (HFD) intake,
body weight, running wheel activity (RWA) as well as thermogenesis in brown adipose tissue (BAT) and lipid metabolism in white adipose tissue (WAT). Limited time availability of food and continuous access to running wheels led to
anorexia and significantly reduced
body weight.
THC treatment (0.5 and 2.0 mg/kg/day) transiently stimulated chow intake with a moderate effect on RWA.
THC (2.0 mg/kg/day) significantly reduced
body weight loss and shifted markers of thermogenesis in BAT and lipid metabolism in WAT in directions consistent with reduced energy expenditure and lipolysis.
THC (2.0 mg/kg/day) combined with HFD, produced a transient increase in food intake, reduction in RWA, attenuation of
body weight loss, and changes in markers of thermogensis in BAT and lipolysis in the WAT. These changes were significantly greater than those seen in vehicle (HFD), vehicle (chow), and
THC (chow)-treated animals. These data show for the first time the effectiveness of the
endocannabinoid system in attenuating the
weight loss associated with the development of ABA via a mechanism involving reduced energy expenditure.