Maternal separation induces long-term changes in mineralocorticoid receptor in rats subjected to chronic stress and treated with tianeptine

Abstract

Purpose: The aim of this study was to analyze whether early maternal separation would result in long-term, persistent alterations in stress response in adulthood, altering mineralocorticoid receptor immunoreactivity (MR-ir) in the dorsal hippocampal areas [CA1, CA2, CA3 and dentate gyrus (DG)], paraventricular nucleus of the hypothalamus and medial and central nucleus of the amygdala, key structures involved in stress response regulation. We also analyzed whether chronic treatment with the antidepressant tianeptine reverses these possible changes.

Material and methods: Male Wistar rats were subjected to daily maternal separation for 4.5 h during 3 weeks or left undisturbed. As adults, they were exposed to chronic stress during 24 days or left undisturbed, and they were also daily treated with tianeptine (10 mg/kg i.p.) or isotonic solution.

Results: In the CA2 and DG areas of the dorsal hippocampus, there was an increase in MR-ir in non-maternally separated and chronic stressed groups. Tianeptine raised MR-ir in the CA3. In the DG, control and maternally separated + chronic stress groups treated with tianeptine showed more MR-ir than their respective vehicle groups. In the paraventricular nucleus, tianeptine decreased MR-ir in non-separated groups, but not in maternally separated rats.

Conclusions: Our results support findings that early-life events induce long-term changes in stress response regulation, persistent into adulthood, which are manifested during challenges in later life, and that treatment with tianeptine, which tends to attenuate the hypothalamus-pituitary-adrenal axis dysregulation, depends on the individual experience of each rat.

Keywords:

• Amygdala
• antidepressant
• hippocampus
• paraventricular nucleus

Acknowledegments

We are grateful to Servier Laboratories S.A. for kindly providing tianeptine sodium salt and to Dr. Gomez-Sanchez for helpfully providing the MR1–18 1D5 antibody.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National University of Córdoba (SECyT) [grant numbers 114/10 and 162/12]; the National Council of Scientific and Technical Research, Argentina [grant PIP CONICET 2013-2015 GI 0597] and Doctoral Fellowship CONICET PhD College of Biological Sciences, Faculty of Exact, Physical and Natural Sciences, National University of Córdoba, Argentina.