Ghrelin, Cannabinoids, and Motivation: Increased Food Motivation on Progressive Ratio Paradigm Through MAGL/FAAH Inhibition in a Rat Model

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De Sante, Stephanie




Both ghrelin and endogenous cannabinoids act in the ventral tegmental area (VTA) to increase feeding behaviours, through their interaction is not understood. It is hypothesized that ghrelin influences this system by stimulating the release of endocannabinoids from dopamine cells through its receptor, via increased synthesis and accumulation of membrane bound cannabinoid enzymes. First, we used a progressive ratio paradigm to examine the behavioural effects of blocking cannabinoid catabolism on ghrelin induced motivated feeding by administering an intra-VTA infusion of cannabinoid degrading enzymes (MAGL/FAAH) inhibitors (MJN110/PF-00457845), followed by ghrelin. Next, we examined the protein level of cannabinoid related enzymes in the VTA following an injection of ghrelin using western blotting. Our results show a significant increase in motivated feeding behaviours in rats that received both the MAGL/FAAH inhibitor cocktail and ghrelin. Interestingly, western blot analyses showed an increase in degrading enzyme MAGL and a decrease in synthesizing enzyme DAGL-a.






Carleton University

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