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      The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

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          Abstract

          Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.

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          The adolescent brain and age-related behavioral manifestations.

          L Spear (2000)
          To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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            Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators.

            Stress begins in the brain and affects the brain, as well as the rest of the body. Acute stress responses promote adaptation and survival via responses of neural, cardiovascular, autonomic, immune and metabolic systems. Chronic stress can promote and exacerbate pathophysiology through the same systems that are dysregulated. The burden of chronic stress and accompanying changes in personal behaviors (smoking, eating too much, drinking, poor quality sleep; otherwise referred to as "lifestyle") is called allostatic overload. Brain regions such as hippocampus, prefrontal cortex and amygdala respond to acute and chronic stress and show changes in morphology and chemistry that are largely reversible if the chronic stress lasts for weeks. However, it is not clear whether prolonged stress for many months or years may have irreversible effects on the brain. The adaptive plasticity of chronic stress involves many mediators, including glucocorticoids, excitatory amino acids, endogenous factors such as brain neurotrophic factor (BDNF), polysialated neural cell adhesion molecule (PSA-NCAM) and tissue plasminogen activator (tPA). The role of this stress-induced remodeling of neural circuitry is discussed in relation to psychiatric illnesses, as well as chronic stress and the concept of top-down regulation of cognitive, autonomic and neuroendocrine function. This concept leads to a different way of regarding more holistic manipulations, such as physical activity and social support as an important complement to pharmaceutical therapy in treatment of the common phenomenon of being "stressed out". Policies of government and the private sector play an important role in this top-down view of minimizing the burden of chronic stress and related lifestyle (i.e. allostatic overload).
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              Tests for emotionality in rats and mice: a review.

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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                06 August 2014
                2014
                : 8
                : 260
                Affiliations
                [1] 1Neuroscience Institute of Castilla y León (INCYL), University of Salamanca Salamanca, Spain
                [2] 2Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca Salamanca, Spain
                [3] 3Department of Physiology and Pharmacology, University of Salamanca Salamanca, Spain
                [4] 4Department of Cell Biology and Pathology, University of Salamanca Salamanca, Spain
                Author notes

                Edited by: Regina M. Sullivan, Nathan Kline Institute and NYU School of Medicine, USA

                Reviewed by: Gregg Stanwood, Vanderbilt University, USA; Manuel Portavella, University of Seville, Spain

                *Correspondence: Dolores E. López, Neuroscience Institute of Castilla y León (INCYL), University of Salamanca, C/ Pintor Fernando Gallego 1, 37007 Salamanca, Spain e-mail: lopezde@ 123456usal.es

                This article was submitted to the journal Frontiers in Behavioral Neuroscience.

                Article
                10.3389/fnbeh.2014.00260
                4123728
                1bc15ff9-7f90-4e85-9208-4e3cd0fcf4b1
                Copyright © 2014 Pereira-Figueiredo, Sancho, Carro, Castellano and López.

                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.

                History
                : 24 May 2014
                : 14 July 2014
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 110, Pages: 13, Words: 11299
                Categories
                Neuroscience
                Original Research Article

                Neurosciences
                behavior,habituation,open field,restrain stress,serotonin,startle
                Neurosciences
                behavior, habituation, open field, restrain stress, serotonin, startle

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