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Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 175619, 6 pages
Research Article

Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

1Department of Anesthesiology, School of Medicine, Jinling Hospital, Nanjing University, No. 305 East Zhongshan Road, Jiangsu Nanjing 210002, China
2Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, No. 321 Zhongshan Road, Jiangsu Nanjing 210008, China
3The PLA 102nd Hospital and Mental Health Center of Military, No. 55 North Heping Road, Jiangsu Changzhou 213000, China

Received 14 January 2012; Revised 6 February 2012; Accepted 8 February 2012

Academic Editor: Daniel T. Monaghan

Copyright © 2012 Chun Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR) in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST). Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.