Effects of tianeptine on adult rats following prenatal stress
Hwayoung Lee 1, Hyung-Ki Kim 1, Jun-Tack Kwon 1, Young Ock Kim 2, Sang Won Lee 2, Sanghyun Lee 3, Ik-Hyun Cho 4, Hak-Jae Kim 1, 5*
1Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, 31151, Republic of Korea., 2Department of development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong,27709, Republic of Korea, 3Department of Integrative Plant Science, Chung-Ang University, Anseong 17546, Republic of Korea, 4Department of Convergence Medical Science, Brain Korea 21 Plus Program, and Institute of Korean Medicine, College of Oriental Medicine, Kyung Hee University, Seoul 02453, Republic of Korea, 5Soonchunhyang Medical Research Institute, College of Medicine, Soonchunhyang University, Cheonan, 31151, Republic of Korea.
Received: March 24, 2017; Revised: May 1, 2017; Accepted: May 25, 2017; Published online: May 25, 2017.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats.
Methods: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies.
Results: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased.
Conclusion: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.
Keywords: Prenatal stress, Animal model, Tianeptine, Haloperidol, Behavior test, Psychiatric disorder


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