Chronic 7,8-Dihydroxyflavone Treatment Reverses Social Deficits And Inflammation In An Animal Model Of Depression

Background: Patients with major depressive disorder display impairment in social behaviors and abnormal inflammatory activities. Increasing evidence indicates that deficiency in brain-derived neurotrophic factor (BDNF) is linked to depression. We hypothesized that neonatal clomipramine (CLI) treatment, an animal model of depression, would result in deficits in social behavior and chronic inflammation and that these alterations could be reversed by activation of high affinity BDNF receptor TrkB.Methods: Male neonatal rats received subcutaneous injection of saline or CLI(20mg/kg, twice/day) during postnatal days (PD) 8-21. CLI-treated rats received intraperitoneal injection of vehicle or chronic 7,8-dihydroxyflavone (7,8-DHF,5mg/kg/day),a TrkB agonist,during PD51-64 (saline-treated rats received vehicle injection during the same period). Social behaviors were determined with three-chambered social approach test on PD65-66. Pro-inflammatory cytokine levels in the serum and brain were measured on PD90.Results: ① CLI treatment reduced motor activity and exploration, impaired social approach, preference and memory; ② CLI treatment decreased body and spleen weights;③ CLI treatment increased interleukin-1beta (IL-lβ), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFa) levels in the serum and hippocampus. ④ These alterations were reversed by 7,8-DHF treatment. ⑤ The serum levels of IL-1β, TNFa and IL-6 were negatively correlated with spleen weight. Hippocampal BDNF levels were positively correlated with spleen weight and negatively correlated with the above cytokines.Conclusion: Our results reveal the presence of social deficits and chronic inflammation the brain and peripheral in an animal model of depression,which can be effectively reversed by chronic 7,8-DHF treatment...