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Cannabinoid CB 1 /CB 2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity‐based anorexia
Author(s) -
Scherma Maria,
Satta Valentina,
Collu Roberto,
Boi Maria Francesca,
Usai Paolo,
Fratta Walter,
Fadda Paola
Publication year - 2017
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13892
Subject(s) - weight loss , cannabinoid receptor agonists , agonist , cannabinoid , leptin , medicine , endocrinology , cannabinoid receptor , anorexia , endocannabinoid system , anorexia nervosa , receptor , pharmacology , obesity , psychiatry , eating disorders
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 the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic‐like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Key Results Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 ‐tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP‐55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Conclusion and Implications Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance.