Original Research ARTICLE

Front. Mol. Neurosci., 10 April 2014 | http://dx.doi.org/10.3389/fnmol.2014.00024

Early-life stress induces persistent alterations in 5-HT1A receptor and serotonin transporter mRNA expression in the adult rat brain

  • 1Grupo de NeuroGastroBioquímica, Laboratorio de Química Biológica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
  • 2Department of Psychiatry, University College Cork, Cork, Ireland
  • 3Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
  • 4Department of Anatomy, University College Cork, Cork, Ireland

Early-life experience plays a major role in the stress response throughout life. Neonatal maternal separation (MS) is an animal model of depression with an altered serotonergic response. We hypothesize that this alteration may be caused by differences in 5-HT1A receptor and serotonin transporter (SERT) mRNA expression in brain areas involved in the control of emotions, memory, and fear as well as in regions controlling the central serotonergic tone. To test this, Sprague–Dawley rats were subjected to MS for 3 h daily during postnatal days 2–12. As control, age matched rats were non-separated (NS) from their dams. When animals reached adulthood (11–13 weeks) brain was extracted and mRNA expression of 5-HT1A receptor in amygdala, hippocampus and dorsal raphé nucleus (DRN) and SERT in the DRN was analyzed through in situ hybridisation. Densitometric analysis revealed that MS increased 5-HT1A receptor mRNA expression in the amygdala, and reduced its expression in the DRN, but no changes were observed in the hippocampus in comparison to NS controls. Also, MS reduced SERT mRNA expression in the DRN when compared to NS rats. These results suggest that early-life stress induces persistent changes in 5-HT1A receptor and SERT mRNA expression in key brain regions involved in the development of stress-related psychiatric disorders. The reduction in SERT mRNA indicates an alteration that is in line with clinical findings such as polymorphic variants in individuals with higher risk of depression. These data may help to understand how early-life stress contributes to the development of mood disorders in adulthood.

Keywords: maternal separation, 5-HT1A receptor, serotonin transporter, amygdala, dorsal raphé nucleus

Citation: Bravo JA, Dinan TG and Cryan JF (2014) Early-life stress induces persistent alterations in 5-HT1A receptor and serotonin transporter mRNA expression in the adult rat brain. Front. Mol. Neurosci. 7:24. doi: 10.3389/fnmol.2014.00024

Received: 10 January 2014; Accepted: 19 March 2014;
Published online: 10 April 2014.

Edited by:

Mathias V. Schmidt, Max Planck Institute of Psychiatry, Germany

Reviewed by:

Gustavo Pacheco-Lopez, Universidad Autónoma Metropolitana, Mexico
Xiao-Dong Wang, Zhejiang University, China

Copyright © 2014 Bravo, Dinan and Cryan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Javier A. Bravo, Grupo de NeuroGastroBioquímica, Laboratorio de Química Biológica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Avenida Universidad 330, Curauma, Valparaíso, Región de Valparaíso, Chile e-mail: javier.bravo@ucv.cl;
John F. Cryan, Department of Anatomy, University College Cork, Western Gateway Building, Cork, Ireland e-mail: j.cryan@ucc.ie