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

BMC Neuroscience

Research Article

Cheol Min Choi¹  Young Hoon Kim²  Jae-Hon Lee³  Yena Lee⁴  Rodrigo B. Mansur⁵  Roger S. McIntyre⁵  Hye Yeon Cho⁶  Mi Kyoung Seo⁶  Chan Hong Lee⁶  Sung Woo Park⁷  Jung Goo Lee⁸ 

[1] Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea;Department of Psychiatry, Gongju National Hospital, Gongju, Republic of Korea;Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea;Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada;Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada;Department of Psychiatry, University of Toronto, Toronto, ON, Canada;Paik Institute for Clinical Research, Inje University, 633-165 Gaegum-dong, Jin-gu, 614-735, Busan, Republic of Korea;Paik Institute for Clinical Research, Inje University, 633-165 Gaegum-dong, Jin-gu, 614-735, Busan, Republic of Korea;Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea;Paik Institute for Clinical Research, Inje University, 633-165 Gaegum-dong, Jin-gu, 614-735, Busan, Republic of Korea;Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea;Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada;Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea;

关键词: Chronic restraint stress;    Hippocampus;    mTOR signaling;    Antidepressants;    Neuroplasticity;   

DOI  :  10.1186/s12868-017-0357-0

 received in 2016-12-01, accepted in 2017-04-20,  发布年份 2017

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY   
© The Author(s) 2017