title: The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia.
abstract: 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.
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC, Australia. aaron.verty@monash.edu
authors.forename: Aaron N A
authors.initials: AN
authors.lastname: Verty
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Evetts
authors.forename: Geraldine J
authors.initials: GJ
authors.lastname: Crouch
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
authors.forename: Aneta
authors.initials: A
authors.lastname: Stefanidis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Oldfield
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000209:etiology* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis / Q000187:drug effects; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol