Chronic clomipramine treatment restores hippocampal expression of glial cell line-derived neurotrophic factor in a rat model of depression.
BACKGROUND
Because there is evidence that certain neurotrophic factors are involved in depression and the mechanism of antidepressant treatment, it is hypothesized that neurotrophic factors may also play a functional role in the etiology of depression and treatment. Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor (TGF-β)-super-family. We performed a study to assess the impact of chronic unpredictable stress (CUS) and clomipramine treatment on GDNF expression in the rat hippocampus.


METHODS
Using a rat model of CUS-induced depression, we administered clomipramine, one of the typical antidepressants, every day for 3 weeks starting 2 weeks after the beginning of the experiment. GDNF level in the hippocampus was detected by immunohistochemsitry, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Behavioral changes were measured by forced swimming test (FST) and open field test (OFT).


RESULTS
Animals exposed to CUS showed depression-like behavior and exhibited a significant decrease in GDNF expression in the hippocampus. Chronic clomipramine treatment reversed the behavioral deficits and the decrease in GDNF levels induced by CUS.


CONCLUSIONS
The relatively small number of the depression-model rats may cause some bias of behavioral tests.


CONCLUSIONS
In our study, chronic clomipramine treatment restored GDNF expression in the hippocampus of CUS-induced depression rats, suggesting that GDNF is involved in the behavioral responses to antidepressants. The beneficial effects of clomipramine suggest that GDNF may be a viable target for new antidepressant drug development.
Department of integrative medicine and neurobiology, Shanghai medical college, Fudan University, Shanghai 200032, PR China.
Qiong
Q
Liu
Hai-Yan
HY
Zhu
Bing
B
Li
Yan-Qing
YQ
Wang
Jin
J
Yu
Gen-Cheng
GC
Wu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*; D013550:Swimming
D000928:Antidepressive Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D002997:Clomipramine