Neuroscience and Neurobiology
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.
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Cao, X., Xu, P., Oyola, M. G., Xia, Y., Yan, X., Saito, K., Zou, F., Wang, C., Yang, Y., Hinton, A., Yan, C., Ding, H., Zhu, L., Yu, L., Yang, B., Feng, Y., Clegg, D. J., Khan, S., DiMarchi, R., … Xu, Y. (2014). Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice. The Journal of Clinical Investigation, 124(10), 4351–4362. https://doi.org/10.1172/JCI74726
Cao, Xuehong; Xu, Pingwen; Oyola, Mario G.; Xia, Yan; Yan, Xiaofeng; Saito, Kenji; Zou, Fang; Wang, Chunmei; Yang, Yongjie; Hinton, Antentor Jr.; Yan, Chunling; Ding, Hongfang; Zhu, Liangru; Yu, Likai; Yang, Bin; Feng, Benjamin; Clegg, Deborah J.; Khan, Sohaib; DiMarchi, Richard; Mani, Shaila K.; Tong, Qingchun; and Xu, Yong, "Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice" (2014). Peer Reviewed Articles. 77.