Cytoprotective effect is one of common action pathways for antidepressants.
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.
Li
Yun-Feng
YF
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. LYF619@yahoo.com.cn
Liu
Yan-Qin
YQ
Huang
Wen-Chao
WC
Luo
Zhi-Pu
ZP
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
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D005473:Fluoxetine; D020932:Nerve Growth Factor; D020912:Moclobemide; D002118:Calcium; D003891:Desipramine; D003345:Corticosterone