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, 16 (2), 197-208

Effects of Tianeptine on Adult Rats Following Prenatal Stress

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Effects of Tianeptine on Adult Rats Following Prenatal Stress

Hwayoung Lee et al. Clin Psychopharmacol Neurosci.

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: Behavior test; Haloperidol; Laboratory animal model; Prenatal stress; Psychiatric disorder; Tianeptine.

Figures

Fig. 1
Fig. 1
Western blot analysis of Dpysl2, Lasp1, and NF-H expression in brains of prenatal stress induced rats. (A) Dpysl2, Lasp1, and NF-H protein expression by Western blotting using Actb as an internal control. PNS rats demonstrated decreased expression of Dpysl2, Lasp1, and NF-H in the frontal cortex. Decreased expression levels of Dpysl2 and Lasp1 were recovered by tianeptine treatment. (B) Scatter gram in the graph indicating standard error mean (SEM) (p<0.05 compared to the prenatal stress group in Lasp1 expression). (C) Scatter gram in the graph indicating SEM (p<0.05 compared to prenatal stress group in Dpysl2 expression). (D) Scatter gram in the graph indicating SEM (p<0.05 compared to prenatal stress group in NF-H expression). NS, non-prenatal stressed offspring; PNS, prenatal stressed offspring; HP, haloperidol treatment offspring; TN, tianeptine treatment offspring. *NS and PNS, **PNS and HP, ***PNS and TN. Data are presented in mean±SEM; p<0.05.
Fig. 2
Fig. 2
Immunohistochemical analysis of NF-H expression in brains of prenatal stress induced rats. (A) Confocal microscopic image showing immunofluorescent staining for NF-H (anti-NF-H, red, Cy3) with NeuN in the frontal cortex. Fluorescent staining revealed decreased NF-H in these regions. Scale bar, FC: 50 μm. (B) Scatter gram in the graph indicating standard error of mean (SEM) (p<0.05 compared to the prenatal stress group in the frontal cortex). FC, frontal cortex; NS, non-prenatal stressed offspring; PNS, prenatal stressed offspring; HP, haloperidol treatment offspring; TN, tianeptine treatment offspring. *NS and PNS, **PNS and HP, ***PNS and TN. Data are presented in mean±SEM; p<0.05.
Fig. 3
Fig. 3
Immunohistochemical analysis of Dpysl2 expression in brains of prenatal stress induced rats. (A) Confocal microscopic image showing immunofluorescent staining for Dpysl2 (anti-Dpysl2, red, Cy3) with NeuN in the frontal cortex. Fluorescent staining revealed decreased Dpysl2 in these regions. Scale bar, FC; 50 μm. (B) Scatter gram in the graph indicating standard error mean (SEM) (p<0.05 compared to prenatal stress group in the frontal cortex). NS, non-prenatal stressed offspring; PNS, prenatal stressed offspring; HP, haloperidol treatment offspring; TN, tianeptine treatment offspring. *NS and PNS, **PNS and HP, ***PNS and TN. Data are presented in mean±SEM; p<0.05.
Fig. 4
Fig. 4
Percent of corticosterone levels in adolescent male rats. These were analyzed for male offspring of rats exposed to stress during gestation in the last behavior test or male rats derived from mothers without stress during gestation. Corticosterone secretion was induced by holding rats in restraint tubes for 60 minutes. Corticosterone levels were increased in the PNS group but decreased in haloperidol or tianeptine treatment groups. NS, non-prenatal stressed offspring; PNS, prenatal stressed offspring; HP, haloperidol treatment offspring; TN, tianeptine treatment offspring. *NS and PNS, **PNS and HP, ***PNS and TN. Data are presented in mean±standard error mean; p<0.05.

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References

    1. Imamura Y, Nakane Y, Ohta Y, Kondo H. Lifetime prevalence of schizophrenia among individuals prenatally exposed to atomic bomb radiation in Nagasaki City. Acta Psychiatr Scand. 1999;100:344–349. doi: 10.1111/j.1600-0447.1999.tb10877.x. - DOI - PubMed
    1. Meyer U, Feldon J. Epidemiology-driven neurodevelopmental animal models of schizophrenia. Prog Neurobiol. 2010;90:285–326. doi: 10.1016/j.pneurobio.2009.10.018. - DOI - PubMed
    1. Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev. 2008;32:1073–1086. doi: 10.1016/j.neubiorev.2008.03.002. - DOI - PubMed
    1. Seckl JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol. 2004;151( Suppl 3):U49–U62. doi: 10.1530/eje.0.151U049. - DOI - PubMed
    1. de Kloet ER, Sibug RM, Helmerhorst FM, Schmidt MV. Stress, genes and the mechanism of programming the brain for later life. Neurosci Biobehav Rev. 2005;29:271–281. doi: 10.1016/j.neubiorev.2004.10.008. - DOI - PubMed
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