title: Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.
abstract: Epidemiological studies suggest that emotional liability in infancy could be a predictor of anxiety-related disorders in the adulthood. Rats exposed to prenatal restraint stress ("PRS rats") represent a valuable model for the study of the interplay between environmental triggers and neurodevelopment in the pathogenesis of anxious/depressive like behaviours. Repeated episodes of restraint stress were delivered to female Sprague-Dawley rats during pregnancy and male offspring were studied. Ultrasonic vocalization (USV) was assessed in pups under different behavioural paradigms. After weaning, anxiety was measured by conventional tests. Expression of GABA(A) receptor subunits and metabotropic glutamate (mGlu) receptors was assessed by immunoblotting. Plasma leptin levels were measured using a LINCOplex bead assay kit. The offspring of stressed dams emitted more USVs in response to isolation from their mothers and showed a later suppression of USV production when exposed to an unfamiliar male odour, indicating a pronounced anxiety-like profile. Anxiety like behaviour in PRS pups persisted one day after weaning. PRS pups did not show the plasma peak in leptin levels that is otherwise seen at PND14. In addition, PRS pups showed a reduced expression of the γ2 subunit of GABA(A) receptors in the amygdala at PND14 and PND22, an increased expression of mGlu5 receptors in the amygdala at PND22, a reduced expression of mGlu5 receptors in the hippocampus at PND14 and PND22, and a reduced expression of mGlu2/3 receptors in the hippocampus at PND22. These data offer a clear-cut demonstration that the early programming triggered by PRS could be already translated into anxiety-like behaviour during early postnatal life.
authors.affiliation: Neuroplasticity Team, UMR 8576 CNRS, North University of Lille, Villeneuve d'Ascq, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Laloux
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.forename: Gilles
authors.initials: G
authors.lastname: Van Camp
authors.forename: Angela
authors.initials: A
authors.lastname: Giovine
authors.forename: Igor
authors.initials: I
authors.lastname: Branchi
authors.forename: Sebastien
authors.initials: S
authors.lastname: Bouret
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bergonzelli
authors.forename: Marithé
authors.initials: M
authors.lastname: Malagodi
authors.forename: Roberto
authors.initials: R
authors.lastname: Gradini
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Muriel
authors.initials: M
authors.lastname: Darnaudéry
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D014828:Vocalization, Animal
chemical_list: D020738:Leptin; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate