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The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL\/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS\u2010like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro\u2010Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma\u2010aminobutyric acid\u2010producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC\u2013LHA GABAergic pathway. Enzyme\u2010linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5\u2010hydroxytryptamine (5\u2010HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS\u2010like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS\u2010like symptoms. The chemogenetic activation of ACC\u2013LHA GABAergic neurons elicited anxiety\u2010like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC\u2013LHA GABAergic neurons alleviated anxiety\u2010like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC\u2013LHA GABAergic pathway in modulating anxiety\u2010like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS\u2010like symptoms.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16150-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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