title: Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.
abstract: Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life.
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gatta
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Reynaert
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, 10065 New York, NY, USA; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Jordan
authors.initials: J
authors.lastname: Marrocco
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
authors.affiliation: Faculté de Médecine de Lille, UDSL, 59045 Lille, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Soichot
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Lucie
authors.initials: L
authors.lastname: Deruyter
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Gilles Van
authors.initials: GV
authors.lastname: Camp
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Hammou
authors.initials: H
authors.lastname: Bouwalerh
authors.affiliation: Azienda Sanitaria Locale, RM.E. Unità Operativa Complessa Adolescent, 00100 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: Dept of Pharmacy, Univ. of Genoa, 16126 Genoa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.affiliation: Faculté de Médecine de Lille, UDSL, 59045 Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; IRCCS Neuromed, 86077 Pozzilli, Italy; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Univ.Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; LIA France/Italy (International Associated Laboratory "Prenatal Stress and Neurodegenerative Diseases", Glycobiology of Stress-related Diseases team, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Neuromed, 86077-Pozzilli, Italy and Sapienza University of Rome, 00185-Rome, Italy. Electronic address: stefania.maccari@univ-lille1.fr.
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000378:metabolism; D012149:Restraint, Physical; D012919:Social Behavior; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D018045:Receptors, Oxytocin; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D010121:Oxytocin; C020731:carbetocin
keywords: Anxiety; Carbetocin; Glutamate; Perinatal stress; Social behavior; Ventral hippocampus