Adolescent escitalopram administration modifies neurochemical alterations in the hippocampus of maternally separated rats

Abstract

Early life stress is a potential precursor of eventual neuropsychiatric diseases and may result in altered neurodevelopment and function of the hippocampus, which thus provides a site at which potential interventions to modify the effects of early life stress may act. In this study, Sprague-Dawley rat pups comprising male and female animals underwent maternal separation (MS) for 180min from postnatal days (PND) 2 to 14, or were left with their dams. They subsequently received daily administration of saline (0.9%), escitalopram (10mg/kg), or no treatment during adolescence (PND 43-60). All adult animals underwent brain magnetic resonance imaging (MRI) and bilateral hippocampal proton magnetic resonance spectroscopy ( 1H-MRS). Neither MS nor escitalopram treatment had a significant effect on hippocampal volume. Adult rats that experienced MS displayed significantly increased choline-containing compounds (Cho) and decreased N-acetylaspartate (NAA), glutamate (Glu) and Myo-inositol (MI) relative to the stable neurometabolite creatine (Cr) in hippocampus. Administration of escitalopram during adolescence could modify the alterations of NAA/Cr, Glu/Cr and MI/Cr. The effects of MS on hippocampal neurochemistry were most significant in the right hippocampus. These results indicate that MS in rats has long-term consequences on hippocampal neurochemistry reflective of neural density/functional integrity, especially on the right hippocampus, and adolescent administration with escitalopram can at least partially ameliorate these neurochemical alterations. Furthermore, these metabolite changes seem to be more sensitive indicators of the results from early life stress than volume changes. © 2010 Elsevier B.V.