Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

摘要: Symptoms of depressive disorders such as anhedonia and despair can be a product an aberrant adaptation to stress conditions. Chronic unpredictable model (CUS) generate increase in the activity hypothalamic-pituitary-adrenal axis (HPA) induce reduction neurotrophin signaling proliferation neural progenitors adult dentate gyrus, together with increased oxidative stress. Levels endocannabinoid anandamide (AEA) seem affect these depression-by-stress-related features could modulated by fatty acid amide hydrolase (FAAH). We aimed evaluate effects FAAH inhibitor, URB597, on depressive-like behavior mice subjected CUS. URB597 was administered intraperitoneally at dose 0.2 mg/kg for 14 days after Depressive-like behaviors, anhedonia, were evaluated splash forced swimming tests, respectively. Alterations HPA level analyzed using relative weight adrenal glands serum corticosterone levels. Oxidative brain-derived neurotrophic factor (BDNF) also evaluated. Fluorescence immunohistochemistry tests performed immunoreactivity BrdU Sox2 colabeling comparison precursors. The administration able reverse generated model. Likewise, other physiological responses associated CUS reduced treated group, among them, glands, stress, decreased BDNF number Most auspicious enzyme inhibitor blocked employing cannabinoid receptor antagonist. In conclusion, chronic inhibition antidepressant effect, promoting progenitor expression, while reducing gland under