Title

 

Authors

P. Fadda^1,2, M. Scherma^1,2, F. Businco¹, C. Dessy¹, AL. Loizedda³ , B. Pigliacampo¹, L. Fattore^{2, 3} and W. Fratta^1,3
 
1B.B. Brodie Department of Neuroscience, University of Cagliari, Cagliari, Italy;
²Center of Excellence ‘Neurobiology of Addiction’;
 ³CNR Institute of Neuroscience-Cagliari, Italy 

 

Abstract

Binge eating disorder (BED) is an intermittent excessive behavior with negative effects on both physical and mental health (APA, 2000). The endocannabinoid system has been shown to control food intake in both animals and humans, modulating either rewarding or quantitative aspects of eating, and those actions are mediated by the CB1 receptors (Matias and Di Marzo, 2007). Both exogenous and endogenous cannabinoids stimulate food intake through several mechanisms, while CB1 receptor blockade decreases food intake and behaviors associated with feeding in many rodent models. Enhanced concentrations of circulating Anandamide (AEA) have been reported in overweight/obese patients with BED (Monteleone et al., 2005) suggesting thatalterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. The aim of this study was to investigate whether the FAAH inhibitor URB597,which magnifies and prolongs the effects of endogenous AEA only in brain areas where it is synthesized and released, and the CB1 receptor antagonist rimonabant may be effective in modulating the aberrant eating behavior present in a validated rat model of binge eating (Corwin et al., 1998).Furthermore, we evaluated the effects of sibutramine, a 5HT and NA uptake inhibitor, which is one of the few possible therapeutic options in BED therapy. Binge-type eating was induced by providing limited access to an optional source of fat dietary (margarine) in female rats that were no food-deprived. Margarine was provided only during a restricted period of time (2hr).Experimental groups were as follows: High Restriction(HR) group, with limited access to margarine on Monday-Wednesday-Friday;Low Restriction (LR) group, with limited access to margarine every day; Control  (C) group, with no access to margarine. In accordance with published data (Dimitriou et al., 2000),  we found that the HR group consumed more margarine during the limited-access on Monday-Wednesday-Fridaycompared to  LR group. However, the chow intake of both groups did not differ from the C group. After the binge behavior reached the stability (3-4 weeks), we started administering the drugs. Pretreatment with URB597 did not significantly change margarine or chow intake in all experimental groups. On the other hand, rimonabant significantly reduced margarine intake in HR group, at doses of 0.3 and 3 mg/kg. Only the dose of 3 mg/kg was able to reduce the margarine intake in the LR group. In addition, at the higher dose (3 mg/kg) rimonabant decreased 2hr chow intake in all groups. Also sibutramine significantly reduced margarine  intake in both groups, but only the higher dose of 3 mg/kg was able to affect the intake behavior in the HR group. In contrast to the effects on margarine, sibutramine decreases 2hr chow intake only in the C group. Our results show that rimonabant can reduce fat intake in rats under binge-type condition, demonstrating an involvement of the endocannabinoid system in binge eating disorders.
 
Matias I, Di Marzo V. (2007) Endocannabinoids and the control of energy balance. Trends Endocrinol Metab. 18: 27-37.
Monteleone et al., (2005) Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia  nervosa.   Neuropsychopharmacology. 30(6):1216-21
Corwin et al., (1998) Limited access to a dietary fat option affects ingestive behavior but not body composition in male rats.Physiol Behav. 65(3):545-53.
Dimitiriou et al., (2000) Effects of limited access to a fat option on food intake and body composition in female rats.Int J Eat Disord.28(4):436-45.