title: 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats.
  
  
  METHODS
  SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured.
  
  
  RESULTS
  Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg.
  
  
  CONCLUSIONS
  7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chang
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan.; Division of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Che-Se
authors.initials: CS
authors.lastname: Tung
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chin-Bin
authors.initials: CB
authors.lastname: Yeh
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
keywords: Anxiety; BDNF; Chronic mild stress; Depression; TrkB agonist