title: Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.
abstract: One of the most peculiar characteristics of the stress response is the pronounced inter-individual and inter-strain variability both in behavioral and neurochemical outcomes. Several studies confirm that rodents belonging to the same or different strain and/or gender, when exposed to a stressor, may show behavioral and cognitive differences. We compared the effects of long-term betamethasone 21-phosphate disodium (BTM), a widely clinically used corticosteroid, on animal behavior and neurogenesis in CD1 and DBA/2 mice. BTM treatment, in CD1 mice, increased body weight gain and anxiety parameters while having pro-depressant effects. Furthermore, BTM significantly reduced neurogenesis in the dentate gyrus of the hippocampus. Finally, BTM treatment induced a significant impairment in memory and learning performance in the Morris water maze. At odds, BTM administration, in DBA/2 mice, caused a significant reduction in the body weight while not modifying anxiety parameters. In addition, both an increased synaptogenesis and neurogenesis were found. Similarly to CD1 mice, also in DBA/2 mice, memory and learning were impaired. Our data confirm that long-term exposure to corticosteroids can generate or aggravate psychiatric/neurologic disorders such as depression, anxiety, memory and learning. Our study did not reveal significant differences between corticosterone and BTM treatment in CD1 mice. In contrast, BTM treatment in mice with an anxious phenotype (DBA/2 mice) revealed some contrasting results indicating that genetic factors can influence corticosteroids dependent effects. Finally, our data further underline the need for a re-evaluation of neurogenesis role; the increased neurogenesis observed in DBA/2 mice and behavioral effects might be distinguished phenomena.
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Aiello
authors.affiliation: Department of Biological and Environmental Science, University of Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: Science of Health Department, School of Pharmacy, University of Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leo
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Chimirri
authors.affiliation: Science of Health Department, School of Pharmacy, University of Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rispoli
authors.affiliation: National Council of Research (CNR), Institute of Neurological Science, Catanzaro, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Marra
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.affiliation: Department of Biological and Environmental Science, University of Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Italy. Electronic address: erusso@unicz.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008869:Microtubule-Associated Proteins; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects; D009479:Neuropeptides; D016622:Silver Staining; D013045:Species Specificity; D018709:Statistics, Nonparametric; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D000089622:Doublecortin Domain Proteins; D005938:Glucocorticoids; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C028994:betamethasone sodium phosphate; D001623:Betamethasone; D001973:Bromodeoxyuridine
keywords: Anxiety; Corticosteroid; Depression; Memory; Neurogenesis; Strain