title: Estrogen, predominantly via estrogen receptor α, attenuates postpartum-induced anxiety- and depression-like behaviors in female rats.
abstract: Contributions from estrogen receptor (ER) subtypes (ERα and ERβ) to postpartum anxiogenic and depressive responses remain unresolved in rats. Using the elevated-plus maze (EPM) and forced swim (FS) tests, we confirmed that primiparous rats exhibited anxiogenic and depressive responses 3 weeks postpartum, improved 5 weeks postpartum (EPM), and recovered at 5 (FS) or 10 weeks postpartum (EPM) compared with diestrus nulliparous females. Immunohistochemistry suggested that these behavioral changes were temporally associated with decreased ERα but not ERβ expression in the medial amygdala (MEA). Additionally, ERα expression in the medial preoptic area (MPOA) significantly increased 10 weeks postpartum. Brain-derived neurotrophic factor (BDNF) expression was significantly elevated in the MEA 3 weeks postpartum. BDNF receptor tropomyosin-related kinase expression was significantly elevated in the MEA at 3 and 10 weeks but not at 5 weeks postpartum. The phosphorylation of ERK (pERK)-2 in the MEA, MPOA, and hippocampal CA1 region was significantly elevated 3 and 5 weeks postpartum. The effects of single daily sc injections of the ERα-selective agonist, propyl pyrazoletriol (PPT); ERβ-selective agonist, diarylpropionitrile; 17β-estradiol (E₂); and vehicle for 6 days in primiparous rats were assessed. PPT and E₂ significantly produced anxiolytic and antidepressant actions in the EPM and FS tests but PPT to a lesser degree than E₂ in the EPM test. Diarylpropionitrile affected the EPM test but was not significantly different from vehicle. BDNF expression was significantly increased 3 weeks postpartum by all treatments in the MPOA but not the CA1 and MEA. E₂ and PPT treatment significantly increased tropomyosin-related kinase and pERK1/2 expression in the MEA and MPOA and increased pERK1/2 expression in the CA1. The onset of anxiety- and depression-like behaviors in postpartum rats may be partly caused by a complex estrogen-mediated mechanism; nevertheless, changes in the ERα-related system, likely in the MEA, are predominantly involved.
authors.affiliation: PhD, Department of Physiology, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan. mfuruta@marianna-u.ac.jp.
authors.forename: Miyako
authors.initials: M
authors.lastname: Furuta
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Shuichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Midori
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Yu
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Akema
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D019052:Depression, Postpartum / Q000188:drug therapy*; D004958:Estradiol / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D020813:Receptor, trkB / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D010636:Phenols; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; D020813:Receptor, trkB