title: Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice.
abstract: Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-α (ERα) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate designed to deliver estrogen to GLP1 receptor-enhanced regions effectively targeted bioactive estrogens to the DRN and substantially suppressed binge-like eating in ovariectomized female mice. Administration of GLP-1 alone reduced binge-like eating, but not to the same extent as the GLP-1-estrogen conjugate. Administration of ERα-selective agonist propylpyrazole triol (PPT) to murine DRN 5-HT neurons activated these neurons in an ERα-dependent manner. PPT also inhibited a small conductance Ca2+-activated K+ (SK) current; blockade of the SK current prevented PPT-induced activation of DRN 5-HT neurons. Furthermore, local inhibition of the SK current in the DRN markedly suppressed binge-like eating in female mice. Together, our data indicate that estrogens act upon ERα to inhibit the SK current in DRN 5-HT neurons, thereby activating these neurons to suppress binge-like eating behavior and suggest ERα and/or SK current in DRN 5-HT neurons as potential targets for anti-binge therapies.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Cao
authors.forename: Pingwen
authors.initials: P
authors.lastname: Xu
authors.forename: Mario G
authors.initials: MG
authors.lastname: Oyola
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yan
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.forename: Fang
authors.initials: F
authors.lastname: Zou
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Yang
authors.forename: Antentor
authors.initials: A
authors.lastname: Hinton
authors.forename: Chunling
authors.initials: C
authors.lastname: Yan
authors.forename: Hongfang
authors.initials: H
authors.lastname: Ding
authors.forename: Liangru
authors.initials: L
authors.lastname: Zhu
authors.forename: Likai
authors.initials: L
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Feng
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
authors.forename: Sohaib
authors.initials: S
authors.lastname: Khan
authors.forename: Richard
authors.initials: R
authors.lastname: DiMarchi
authors.forename: Shaila K
authors.initials: SK
authors.lastname: Mani
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D056912:Binge-Eating Disorder; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D011903:Raphe Nuclei / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D012701:Serotonin; D052216:Glucagon-Like Peptide 1