Cannabinoid CB1/CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia

BACKGROUND AND PURPOSE: Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. EXPERIMENTAL APPROACH: The activity-based anorexia (ABA) rodent model mimics severe body weight loss and increased physical activity, as well as neuroendocrine disturbances (i.e., hypoleptinemia and hypercortisolemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviors and neuroendocrine changes in rats subjected to a repeated ABA regime in order to mimic the human condition in which patients repeatedly undergo recovery and illness cycle. KEY RESULTS: Our data show that subchronic treatment with both the CB1/CB2 receptor natural agonist Δ9-tetrahydrocannabinol and the synthetic CB1/CB2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioral effects were accompanied by an increase in leptin signaling and a decrease in plasma levels of corticosterone. CONCLUSION AND IMPLICATIONS: Taken together, our results further demonstrate EC system involvement in AN pathophysiology and that strategies which modulate EC signaling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance