title: A representative prescription for emotional disease, Ding-Zhi-Xiao-Wan restores 5-HT system deficit through interfering the synthesis and transshipment in chronic mild stress-induced depressive rats.
abstract: BACKGROUND
  Ding-Zhi-Xiao-Wan (DZ, also known as Kai-Xin-San) is a famous traditional Chinese medicine used for the treatment of emotional disease. Previously, we have found that in a variety of animal models of depression (such as tail suspension model, model of chronic fatigue and forced swimming model) DZ demonstrated significant antidepressant behavior and promoted the production of 5-hydroxytryptamine (5-HT). However, the mechanisms of 5-HT regulation are still unclear. Therefore, the current study is designed to further investigate the antidepressant effect of DZ by observing its influence on 5-HT synthesis, metabolism, transport and other key links, so as to clarify the molecular mechanism of its 5-HT regulation.
  
  
  METHODS
  Solitary rising combined with the chronic unpredictable mild stress (CMS) was used to establish the rat model of depression. The rats were given DZ for 3 weeks, the behavior change and the following items in hippocampus and prefrontal cortex were detected simultaneously: 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and 5-HT transporter (5-HTT) were observed.
  
  
  RESULTS
  Our results showed that treatment with the DZ significantly improved the behavior and simultaneously increased the 5-HT level in the hippocampus, prefrontal cortex tissues and hippocampus extracellular of depressive rats. In future studies revealed that DZ could significantly increase the protein and mRNA expression of the key enzymes TPH during the 5-HT synthesis process in the hippocampus and prefrontal cortex of the depressed rats, and suppress the expression of 5-HTT protein and mRNA at the same time. But it had no effects on MAO-A and MAO-B activities.
  
  
  CONCLUSIONS
  We believe that antidepressant effect of DZ is caused by the increase of 5-HT synthesis and reduction of 5-HT re-uptake, and eventually increase the content of 5-HT in the brain and the synaptic gaps.
authors.affiliation: Department of Clinical Pharmacology, General Hospital of Chinese PLA, 28# Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Xian-Zhe
authors.initials: XZ
authors.lastname: Dong
authors.forename: Zhao-Liang
authors.initials: ZL
authors.lastname: Li
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zheng
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Mu
authors.forename: Gang-qiang
authors.initials: GQ
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005518:Food Preferences; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013395:Sucrose; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; C000605449:Kai-Xin-San; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013395:Sucrose; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase
keywords: 5-HT; Depression; Ding-Zhi-Xiao-Wan; Re-uptake; Synthesis