Recovery of hippocampal cell proliferation and BDNF levels, both of which are reduced by repeated restraint stress, is accelerated by chronic venlafaxine.
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.
Xu
H
H
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada SK S7N 5E4.
Luo
C
C
Richardson
J S
JS
Li
X M
XM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D003511:Cyclohexanols / Q000008:administration & dosage*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride
D019208:Brain-Derived Neurotrophic Factor; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride