title: Angiotensin II type 2 receptor signaling affects dopamine levels in the brain and prevents binge eating disorder.
abstract: BACKGROUND
  Binge eating disorder (BED) is associated with dopaminergic activation as food reward, resulting in metabolism-related disorders. Stimulation of angiotensin type 2 (AT2) receptor is reported to inhibit dopamine synthesis. We investigated the possible roles of AT2 receptor-mediated dopamine regulation in the pathogenesis of BED.
  
  
  METHODS
  Male C57BL/6 mice, type 2 diabetic (KKAy) mice and AT2 receptor-null (AT2KO) mice at eight weeks old were treated with AT2 receptor agonist, compound 21 (C21) or saline for two weeks. Mice were subjected to fasting for two days followed by re-feeding for seven days.
  
  
  RESULTS
  Treatment with C21 attenuated the rebound proportion of body weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT2KO mice. Dopamine concentration in the striatum was further increased by fasting in KKAy and AT2KO mice. Administration of C21 significantly attenuated this fasting-induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2 expression in the substantia nigra were markedly lower in KKAy mice compared with C57BL/6 mice, while administration of C21 increased their expression in KKAy mice.
  
  
  CONCLUSIONS
  Our study suggests that AT2 receptor stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan mmogi@m.ehime-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Kan-No
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Kousei
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Chisaka
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Bai
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Bao-Shuai
authors.initials: BS
authors.lastname: Shan
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kukida
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D056912:Binge-Eating Disorder / Q000378:metabolism*; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005215:Fasting; D017353:Gene Deletion; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D015398:Signal Transduction; D013599:Systole; D015430:Weight Gain
chemical_list: D044139:Receptor, Angiotensin, Type 2; D011954:Receptors, Dopamine; D004298:Dopamine
keywords: Angiotensin II type 2 receptor stimulation; binge eating disorder; dopamine; dopamine resistance; weight rebound