title: Cytoprotective effect is one of common action pathways for antidepressants.
abstract: OBJECTIVE
  To explore the possible common action mechanism of antidepressants.
  
  
  METHODS
  The cell viability was detected by MTT assay. The intracellular Ca2+ concentration ([Ca2+]i) was measured by Fura 2-AM fluorescence labeling assay. Using RT-PCR, the mRNA level of nerve growth factor (NGF) was also detected.
  
  
  RESULTS
  High concentration of corticosterone (0.2 mmol/L) was incubated with PC12 cells to simulate the lesion state of brain neurons in depressive illness. Three main kinds of antidepressants used in clinic [(1) tricyclic antidepressants (TCAs), such as desipramine (DIM) 0.625-10 micromol/L; (2) selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FLU) 0.625-10 micromol/L; (3) monoamine oxidase inhibitors (MAOIs), such as moclobemide (MOC) 2.5-40 micromol/L] protected cells from the lesion induced by corticosterone. While antipsychotic drug chlorpromazine or anxiolytic agent diazepam 0.4-50 micromol/L had no such effect. Moreover, DIM 1, 5 micromol/L or FLU 1, 5 micromol/L attenuated the [Ca2+]i overload induced by corticosterone 0.1 mmol/L for 48 h in PC12 cells. Furthermore, treatment with DIM or FLU 10 micromol/L for 48 h elevated the NGF mRNA expression in PC12 cells.
  
  
  CONCLUSIONS
  Despite a remarkable structural diversity, the cytoprotective effect can be viewed as the common action pathway of the antidepressants. Moreover, attenuation of the intracellular Ca2+ overload and elevation of neurotrophic factor (such as NGF) expression is one of the mechanisms of cytoprotective effect of antidepressants.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. LYF619@yahoo.com.cn
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Li
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Liu
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Huang
authors.forename: Zhi-Pu
authors.initials: ZP
authors.lastname: Luo
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003345:Corticosterone / Q000037:antagonists & inhibitors; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D020912:Moclobemide / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D005473:Fluoxetine; D020932:Nerve Growth Factor; D020912:Moclobemide; D002118:Calcium; D003891:Desipramine; D003345:Corticosterone