title: Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades.
abstract: Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan; Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Terada
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan. Electronic address: n.izumo@hamayaku.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Izumo
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan.
authors.forename: Biora
authors.initials: B
authors.lastname: Suzuki
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Karube
authors.affiliation: Division of Gene Expression Mechanisms, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-Ku, Yokohama, Kanagawa 245-0066, Japan; Division of Development Higher Brain Functions (University of Fukui), United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Division of Gene Expression Mechanisms, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kameyama
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Division of Gene Expression Mechanisms, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Division of Development Higher Brain Functions (University of Fukui), United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Division of Development Higher Brain Functions (University of Fukui), United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Division of Gene Expression Mechanisms, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Electronic address: manabe@fujita-hu.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Manabe
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D003907:Dexamethasone; D016666:Fluvoxamine
keywords: Depression; Dexamethasone; Fluvoxamine; HPA axis