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-beta)-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. Method: 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. Limitation: The relatively small number of the depression-model rats may cause some bias of behavioral tests. Conclusion: 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. (C) 2012 Elsevier B. V. All rights reserved.