title: Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats.
abstract: The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption-contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease.
authors.affiliation: School of Animal Biology, Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Nathanael J
authors.identifier: http://orcid.org/0000-0003-2742-6952
authors.initials: NJ
authors.lastname: Yates
authors.affiliation: School of Anatomy, Physiology, and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Donald
authors.initials: D
authors.lastname: Robertson
authors.affiliation: School of Animal Biology, Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodger
authors.affiliation: School of Medicine and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Martin-Iverson
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D001303:Auditory Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology*; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009483:Neuropsychological Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013216:Reflex, Startle / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: C000607792:DRD2 protein, rat; D005938:Glucocorticoids; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003907:Dexamethasone