title: Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression.
abstract: BACKGROUND
  Previous studies from our laboratory indicated that both acute and subchronic administration of Fructus Akebiae (FAE) [the fruit of Akebiae quinata (Thunb.) Decne, (Lardizabalaceae)] produce antidepressant-like effects in animal depressive behavior tests. FAE contains approximately 70% of hederagenin (HG) as its main chemical component.
  
  
  OBJECTIVE
  This study compared the antidepressant ability of FAE with that of HG in mice and further investigated the antidepressant-like effects and potential mechanisms of HG in rats subjected to unpredictable chronic mild stress (UCMS).
  
  
  METHODS
  Mice received FAE (50 mg/kg) and HG (20 mg/kg) once a day via intragastric administration (i.g.) for 3 weeks. The anxiolytic and antidepressant activities of FAE and HG were compared using elevated plus maze (EPM) and behavioral despair tests including tail suspension test (TST) and forced swimming test (FST), respectively. Antidepressant effects of HG (5 mg/kg) were assessed using the UCMS depressive rat model. Moreover, the levels of monoamine neurotransmitters and relevant gene expression in UCMS rats' hippocampi were determined through high-performance liquid chromatography with electrochemical detection and real-time polymerase chain reaction techniques.
  
  
  RESULTS
  The results of our preliminary screening test suggest that HG at 20 mg/kg, while not FAE at 50 mg/kg, significantly decreased the immobility in both TST and FST compared with the vehicle group when administered chronically; however, there were no significant differences observed between the HG and the FAE group. Chronic administration of HG failed to significantly reverse the altered crossing and rearing behavioral performance, time spent in the open arm and closed entries in the EPM, even if they showed an increased tendency, but HG significantly increased the percent of sucrose preference in the sucrose preference test (SPT) and decreased the immobility time in the FST. HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). However, there were no significant differences in the expression of the brain-derived neurotrophic factor.
  
  
  CONCLUSIONS
  These findings confirm the antidepressant-like effects of HG in a behavioral despair test and UCMS rat model, which may be associated with monoamine neurotransmitters and 5-HTT mRNA expression.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou , PR China and.
authors.forename: Bao-Fang
authors.initials: BF
authors.lastname: Liang
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.forename: Ming-Zi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Hai-Biao
authors.initials: HB
authors.lastname: Guo
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Cheng
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Xu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; C571811:Fructus Akebiae; D012701:Serotonin; D009828:Oleanolic Acid; C025763:hederagenin; D009638:Norepinephrine
keywords: BDNF; Fructus Akebiae extracts; serotonin transport protein