Effects of escitalopram and paroxetine on mTORC1 signaling in the rat hippocampus under chronic restraint stress

依他普仑和帕罗西汀对慢性束缚应激大鼠海马mTORC1信号的影响

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作者:Mi Kyoung Seo, Cheol Min Choi, Roger S McIntyre, Hye Yeon Cho, Chan Hong Lee, Rodrigo B Mansur, Yena Lee, Jae-Hon Lee, Young Hoon Kim, Sung Woo Park, Jung Goo Lee

Background

Recent studies have suggested that the activation of mammalian target of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore, the present study evaluated whether antidepressant drugs would exert differential effects on mTOR signaling in the rat hippocampus under conditions of chronic restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for 6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg) administered after the chronic stress procedure. Western blot analyses were used to assess changes in the levels of phospho-Ser2448-mTOR, phospho-Thr37/46-4E-BP-1, phospho-Thr389-p70S6 K, phospho-Ser422-eIF4B, phospho-Ser240/244-S6, phospho-Ser473-Akt, and phospho-Thr202/Tyr204-ERK in the hippocampus.

Conclusion

These findings provide further data that contribute to understanding the possible relationships among mTOR activity, stress, and antidepressant drugs.

Results

Chronic restraint stress significantly decreased the levels of phospho-mTOR complex 1 (mTORC1), phospho-4E-BP-1, phospho-p70S6 K, phospho-eIF4B, phospho-S6, phospho-Akt, and phospho-ERK (p < 0.05); the administration of escitalopram and paroxetine increased the levels of all these proteins (p < 0.05 or 0.01). Additionally, chronic restraint stress reduced phospho-mTORC1 signaling activities in general, while escitalopram and paroxetine prevented these changes in phospho-mTORC1 signaling activities.

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