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Recovery of hippocampal cell proliferation and BDNF levels, both of which are reduced by repeated restraint stress, is accelerated by chronic venlafaxine

The Pharmacogenomics Journal volume 4, pages 322–331 (2004)Cite this article

ABSTRACT

The present study investigated the poststress (PS) cellular and molecular changes in the hippocampus of rats subjected to repeated restraint stress (RS) and the effects of chronic administration of an antidepressant drug, venlafaxine, on these changes. It was found that RS suppressed hippocampal cell proliferation, decreased brain-derived neurotrophic factor (BDNF) levels, and increased both the levels of copper/zinc superoxide dismutase (Cu/Zn-SOD) and the number of Cu/Zn-SOD immunostained hippocampal interneurons. In venlafaxine-treated rats, the changes in cell proliferation, BDNF levels, and the number of Cu/Zn-SOD interneurons returned to control levels on PS Days 21, 14, 7, respectively. In vehicle-injected rats, BDNF and the number of Cu/Zn-SOD interneurons returned to control levels on PS Days 21 and 14, respectively, but cell proliferation was still suppressed on PS Day 21. The stress-induced elevation of Cu/Zn-SOD protein remained during the 3-week PS period, and it was further increased by about 20% after 3 weeks of venlafaxine administration.

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Acknowledgements

This work was supported by Saskatchewan Health, Canadian Psychiatric Research Foundation, Royal University Hospital Foundation, and a CIHR/Rx & D Postdoctoral Fellowship (HX). The authors are grateful to Gabriel Stegeman for her excellent technical assistance. We thank Drs Sergey Fedoroff, Augusto V Juorio, and Vern Bennett for their helpful comments during the preparation of this manuscript.

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  1. Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, S7N 5E4, SK, Canada

    H Xu, C Luo, J S Richardson & X M Li

  2. Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, S7N 5E5, SK, Canada

    J S Richardson

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Correspondence to X M Li.

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Xu, H., Luo, C., Richardson, J. et al. Recovery of hippocampal cell proliferation and BDNF levels, both of which are reduced by repeated restraint stress, is accelerated by chronic venlafaxine. Pharmacogenomics J 4, 322–331 (2004). https://doi.org/10.1038/sj.tpj.6500265

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