Possible protective effects of FAAH inhibition on depressive-like and anxiety-like neurofunctional alterations induced by the abstinence from a high-caloric-high-palatable diet causing obesity

The aim of this study was to explore whether the abstinence from a high-fat-high-palatable diet, causing obesity development, could produce in rodents alterations of emotional reactivity and mood tone and whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH), which increase brain acylethanolamide tone, could ameliorate such alterations. We used a rat model of diet-induced obesity based on a cafeteria-style diet. After the first 40 days of cafeteria diet, rats underwent an abstinence period of 28 days; during this period, half of the animals were chronically treated with the FAAH inhibitor PF-3845 (10 mg/kg, intraperitoneally). At the end of the abstinence, rats were subjected to behavioral tests such as the open field test, the elevated plus maze and the forced swimming test, then sacrificed. Brains were collected, microdissected and selected regions were subjected to HPLC analysis of monoammines and western blot analysis for the expression of proteins of the endocannabinoid system and inflammation were performed. Rats, after cafeteria diet abstinence, revealed an anxiety-like behaviour; PF-3845 was able to exert an anxiolytic-like and antidepressant-like effect. Moreover, numerous alterations of the monoaminergic transmission were detected in selected brain areas and such alterations were partially recovered by the pharmacological treatment. Abstinence was able to alter the expression of proteins involved in neuroinflammation and those affecting the endocannabinoid system. PF-3845 treatment was able to partially restore these alterations. The results support the hypothesis that FAAH might be a possible target for the treatment of psychiatric alterations associated to obesity and food dependence.