{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:43:16Z","timestamp":1789616596221,"version":"build-2803163510"},"reference-count":66,"publisher":"S. Karger AG","issue":"7","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects. <\/jats:p>","DOI":"10.1159\/000538582","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T21:00:26Z","timestamp":1714078826000},"page":"605-622","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with 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