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

• Main Authors: 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
• Format: Article
• Language: English
• Published: BMC 2017-04-01
• Series: BMC Neuroscience
• Subjects: Chronic restraint stress; Hippocampus; mTOR signaling; Antidepressants; Neuroplasticity
• Online Access: http://link.springer.com/article/10.1186/s12868-017-0357-0

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