Activity-based anorexia in C57/BL6 mice: Effects of the phytocannabinoid, △ 9 -tetrahydrocannabinol (THC) and the anandamide analogue, OMDM-2 David Y. Lewis ⁎ , Ros R. Brett Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK Received 7 December 2009; received in revised form 27 March 2010; accepted 2 April 2010 KEYWORDS Activity-based anorexia; Anorexia nervosa; Mice; Tetrahydrocannabinol; OMDM-2 Abstract The activity-based anorexia (ABA) paradigm is one of the few animal models of human anorexia nervosa. We present here the translation of this approach to C57/BL6 mice, a common background for genetically modified mice, and investigate the effects of the cannabinoid agonist, Δ 9 -tetrahydrocannabinol (THC) and the endocannabinoid uptake inhibitor, OMDM-2 in this model. The ABA paradigm was optimised so that food-restricted wheel-running mice displayed anorexia, reduced body weight and disrupted activity and circadian cycles. These conditions produced a murine ABA model with a defined stage and stability to allow for pharmacological intervention. Daily Δ 9 -THC (0.5 mg/kg) decreased survival in the ABA animals but increased feeding in the survivors, OMDM-2 (3 mg/kg) increased food intake, but not sufficiently to reverse weight loss. The effects of this model on endocannabinoid tone in the brain remain to be determined. Since the endocannabinoid system may be implicated in anorexia nervosa and in view of the positive modulation by cannabinoids of some aspects of ABA in this study, further investigation of the effects of cannabinoids in ABA is warranted. © 2010 Elsevier B.V. and ECNP. All rights reserved. 1. Introduction Anorexia nervosa is a disorder of complex aetiology, in which genetic, biological, psychological and socio-cultural factors appear to contribute to susceptibility. No single risk factor appears necessary or sufficient to express the disorder. This has led to difficulties in developing an appropriate model for anorexia nervosa and consequently effective pharma- cotherapies have remained elusive. Anorexia is currently managed by hospitalisation with cognitive behavioural therapy; however prognosis for patients remains poor (Steinhausen, 2002). Paradigms have focussed on mimicking aspects of the human condition. The main characteristics of anorexia nervosa are: decreased food intake, decreased body weight, increased activity, abnormal endocrine func- tion, adolescent onset and predominance in females. Of the models, activity-based anorexia (ABA) seems to mirror these ⁎ Corresponding author. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. 0924-977X/$ - see front matter © 2010 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2010.04.002 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2010) 20, 622–631