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. 2012:2012:175619.
doi: 10.1155/2012/175619. Epub 2012 Apr 8.

Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex

Chun Yang  1 , Wen-Yuan Li, Hai-Yin Yu, Zhi-Qin Gao, Xiang-Liu Liu, Zhi-Qiang Zhou, Jian-Jun Yang
Affiliations

Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex

Chun Yang et al. J Biomed Biotechnol. 2012.

Abstract

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.

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Figures

Figure 1
Figure 1
Immobility time of rats (n = 10) during the FST after intraperitoneal injection of tramadol at different doses. Tramadol administered at the dose of 10 mg/kg significantly decreased the immobility time as compared to saline (*P < 0.05), while tramadol administered at the doses of 2.5 and 5 mg/kg both did not affect the immobility time (P > 0.05).
Figure 2
Figure 2
(a) The scores of crossings of rats (n = 10) during open-field tests. Ketamine administered at the dose of 10 mg/kg did not affect the scores of crossings, and pretreatment with 5 mg/kg tramadol did not affect any changes of scores of crossings (P > 0.05). (b) The scores of rearings of rats (n = 10) during open-field tests. Ketamine administered at the dose of 10 mg/kg did not affect the scores of rearings, and pretreatment with 5 mg/kg tramadol did not affect any changes of scores of rearings (P > 0.05).
Figure 3
Figure 3
The immobility time of rats (n = 10) during the FST after intraperitoneal injection of ketamine and pretreatment with tramadol. Ketamine administered at the dose of 10 mg/kg significantly decreased the immobility time as compared with control (*P < 0.05), and pretreatment with 5 mg/kg tramadol significantly decreased the immobility time as compared with ketamine administration (#P < 0.05).
Figure 4
Figure 4
The expression of p-mTOR in rat hippocampus (n = 3). Ketamine administered at the 10 mg/kg significantly increased the expression of p-mTOR in rat hippocampus as compared with control (*P < 0.05), and tramadol pretreated at the dose of 5 mg/kg significantly increased the expression of p-mTOR as compared with ketamine administered alone (#P < 0.05).
Figure 5
Figure 5
The expression of p-mTOR in rat prefrontal cortex (n = 3). Ketamine administered at the 10 mg/kg significantly increased the expression of p-mTOR in rat prefrontal cortex as compared with control (*P < 0.05), and tramadol pretreated at the dose of 5 mg/kg significantly increased the expression of p-mTOR as compared with ketamine administered alone (#P < 0.05).
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