title: Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains.
abstract: The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes.
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain. Electronic address: cristobal.delrio@uab.cat.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Río-Álamos
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Oliveras
authors.affiliation: Department of Life and Environmental Sciences, Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, 09124 Cagliari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Piludu
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain; Department of Life and Environmental Sciences, Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, 09124 Cagliari, Italy; Servei de RMN, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain; Centro de investigacion Biomédica en Red - Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gerbolés
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Toni
authors.initials: T
authors.lastname: Cañete
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Blázquez
authors.affiliation: Servei de RMN, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain; Centro de investigacion Biomédica en Red - Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lope-Piedrafita
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Martínez-Membrives
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Torrubia
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain.
authors.forename: Adolf
authors.initials: A
authors.lastname: Tobeña
authors.affiliation: Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain. Electronic address: Albert.Fernandez.Teruel@uab.cat.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Teruel
mesh_terms: D000679:Amygdala / Q000000981:diagnostic imaging* / Q000254:growth & development; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D001362:Avoidance Learning; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000254:growth & development; D003345:Corticosterone / Q000097:blood; D006234:Handling, Psychological; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000254:growth & development; D008297:Male; D009929:Organ Size; D011388:Prolactin / Q000097:blood; D066244:Proton Magnetic Resonance Spectroscopy; D011897:Random Allocation; D051381:Rats; D055139:Sensory Gating; D013045:Species Specificity; D013315:Stress, Psychological / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*
chemical_list: D011388:Prolactin; D003345:Corticosterone
keywords: Amygdala volume; Anxiety; Hippocampus volume; Neonatal handling; Roman high- and low-avoidance rats; Sensorimotor gating