title: Prenatal stress and subsequent exposure to chronic mild stress in rats; interdependent effects on emotional behavior and the serotonergic system.
abstract: Exposure to prenatal stress (PS) can predispose individuals to the development of psychopathology later in life. We examined the effects of unpredictable chronic mild stress (CMS) exposure during adolescence on a background of PS in male and female Sprague-Dawley rats. PS induced more anxiety-like behavior in the elevated zero maze in both sexes, an effect that was normalized by subsequent exposure to CMS. Moreover, PS was associated with increased depression-like behavior in the forced swim test in males only. Conversely, sucrose intake was increased in PS males, whilst being decreased in females when consecutively exposed to PS and CMS. Hypothalamo-pituitary-adrenal (HPA) axis reactivity was affected in males only, with higher stress-induced plasma corticosterone levels after PS. Markedly, CMS normalized the effects of PS on elevated zero maze behavior as well as basal and stress-induced plasma corticosterone secretion. At the neurochemical level, both PS and CMS induced various sex-specific alterations in serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) immunoreactivity in the dorsal raphe nucleus, hippocampus and prefrontal cortex with, in line with the behavioral observations, more profound effects in male offspring. In conclusion, these findings show that prenatal maternal stress in Sprague-Dawley rats induces various anxiety- and depression-related behavioral and neuroendocrine changes, as well as alterations in central 5-HT and TPH2 function, predominantly in male offspring. Moreover, CMS exposure partially normalized the effects of previous PS experience, suggesting that the outcome of developmental stress exposure largely depends on the environmental conditions later in life and vice versa.
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON); Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Laboratory of Translational Neuroscience, University of Würzburg, Würzburg, Germany. Electronic address: d.vandenhove@maastrichtuniversity.nl.
authors.forename: D L A
authors.initials: DL
authors.lastname: Van den Hove
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: N K
authors.initials: NK
authors.lastname: Leibold
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: E
authors.initials: E
authors.lastname: Strackx
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: M
authors.initials: M
authors.lastname: Martinez-Claros
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON); Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Laboratory of Translational Neuroscience, University of Würzburg, Würzburg, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: H W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: K R J
authors.initials: KR
authors.lastname: Schruers
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. European Graduate School of Neuroscience (EURON).
authors.forename: J
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D052636:Allostasis; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D001522:Behavior, Animal; D003863:Depression / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D011903:Raphe Nuclei / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012727:Sex Characteristics; D013312:Stress, Physiological; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
keywords: Anxiety; Depression; Pregnancy stress; Serotonin (5-HT); Tryptophan hydroxylase 2 (TPH2)