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Impulsive\u2010like behaviors and a decline in cognitive function were observed in the mouse model of PND established through tibial fracture surgery, accompanied by increased activity of astrocytes in the hippocampal CA1 region. Additionally, transcriptome sequencing revealed increased expression of nicotinic acetylcholine receptors (nAChRs) in PND. In this study, we aimed to investigate the role of nAChRs in the pathogenesis of PND in aging mice. In 18\u2010month\u2010old male C57BL\/6 mice, a PND model was established by tibial fracture surgery, and brain tissues were collected for transcriptomic sequencing 24\u2009h post\u2010surgery. Behavioral assessments of PND mice were conducted using open field, light\u2013dark box, and fear conditioning tests. An nAChRs inhibitor, Adiphenine (125\u2009nM per day), was administered daily for 7\u2009days via intracerebroventricular microinfusion. Pathological changes were observed using immunofluorescence staining and Western blotting, and hippocampal CA1 spikes activity and local field potentials (LFP) were monitored with a microelectrode array. Transcriptomic sequencing of the brains of PND mice revealed upregulation of Cholinergic Receptor Nicotinic Beta 2 Subunit (Chrnb2) and Cholinergic Receptor Nicotinic Beta 4 Subunit (Chrnb4). Additionally, there was an increase in neuronal spikes and enhanced LFP power in the hippocampal CA1 region, along with an increase in the number and morphological changes of astrocytes. Adiphenine was able to inhibit tibial surgery\u2010induced impulsive\u2010like behaviors, but it showed no significant improvement in cognitive function. It also reduced spikes firing and LFP power in the CA1 region. Our study revealed that anesthesia and surgery\u2010induced PND models exhibit impulsive\u2010like behaviors and cognitive impairment. Astrocyte activation and elevated Vglut1 expression may be contributing factors, with nAChRs likely playing an initiating role in this process. Adiphenine can improve impulsive\u2010like behaviors by inhibiting nAChRs.<\/jats:p>\n                  <jats:p>\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\/jnc70190-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70190","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T12:37:52Z","timestamp":1754570272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adiphenine Alleviates Impulsive\u2010Like Behaviors in Aged Mice by Inhibiting Nicotinic Acetylcholine Receptors"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6088-512X","authenticated-orcid":false,"given":"Heng\u2010Yue","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital)  Cangzhou China"},{"name":"Department of Anesthesiology, School and Hospital of Stomatology China Medical University  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Long","family":"Gao","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"},{"name":"Department of Urology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u2010Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital)  Cangzhou China"},{"name":"Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Meng","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital)  Cangzhou China"},{"name":"Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation  Cangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Tao","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital)  Cangzhou 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