mjn110 and Anorexia

Stress is known to reduce food intake. Many aspects of the stress response and feeding are regulated by the endocannabinoid system, but the roles of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in stress-induced anorexia are unclear.. Effects of acute restraint stress on endocannabinoids were investigated in male Sprague-Dawley rats. Systemic and central pharmacological inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) was used to assess the effects of elevated AEA and 2-AG on homeostatic feeding and on food consumption after stress. Animals were pretreated with the FAAH inhibitor, PF-04457845, or the MAGL inhibitor, MJN110, before 2 h acute restraint stress or 2 h homecage period without food.. Restraint stress decreased hypothalamic and circulating AEA, with no effect in the gastrointestinal tract, while 2-AG content in the jejunum (but not duodenum) was reduced. PF-04457845 (30 μg), given i.c.v., attenuated stress-induced anorexia via CB. Our data reveal diverse roles for 2-AG and AEA in homeostatic feeding and changes in energy intake following stress.

Topics: Amidohydrolases; Animals; Anorexia; Arachidonic Acids; Carbamates; Duodenum; Eating; Endocannabinoids; Glycerides; Homeostasis; Jejunum; Male; Monoacylglycerol Lipases; Polyunsaturated Alkamides; Rats, Sprague-Dawley; Stress, Psychological; Succinimides