{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:57:44Z","timestamp":1791493064295,"version":"4.3.4"},"reference-count":42,"publisher":"IMR Press","issue":"11","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project supported by the Natural Science Foundation of Fujian","award":["2018J0838"],"award-info":[{"award-number":["2018J0838"]}]},{"name":"Sailing Fund Project","award":["2021QH1002"],"award-info":[{"award-number":["2021QH1002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: Parkinson\u2019s disease (PD) is characterized by progressive dopaminergic neurodegeneration. Melatonin (MLT) is implicated in neuroprotection, yet the effects of modulating its receptors remain unclear. This study investigated the impact of the MLT receptor agonist agomelatine (AG) and antagonist luzindole (LU) on motor behavior, serum MLT levels, and dopaminergic neuron survival in a 6-hydroxydopamine (6-OHDA) rat model of PD. Methods: A PD model was induced by stereotaxic injection of 6-OHDA into the medial forebrain bundle. Rats received intraperitoneal AG or LU for 2 or 4 weeks. Motor function was assessed using the apomorphine-induced rotation test. Tyrosine hydroxylase (TH) and MLT receptor (MEL-1A\/B) expression in the substantia nigra and striatum were evaluated by immunohistochemistry and Western blot. Serum MLT concentrations were measured using ELISA. Pearson\u2019s correlation analysis was performed to examine associations among serum MLT levels, TH expression, and motor performance. Results: AG significantly improved motor function, increased serum MLT levels, and enhanced TH expression in PD rats. LU also mitigated motor deficits and preserved dopaminergic neurons, despite reducing serum MLT levels. Correlation analysis revealed a dynamic temporal relationship between MLT levels, behavioral outcomes, and dopaminergic neuron survival, indicating that MLT signaling may differentially influence PD pathology at various stages. Conclusions: Both AG and LU demonstrated neuroprotective potential in 6-OHDA\u2013induced PD rats. AG may exert its effects by enhancing endogenous MLT signaling, while LU may protect neurons by modulating excessive MLT activity. These findings highlight the complex regulatory role of the MLT pathway in PD progression and suggest stage-dependent therapeutic benefits of MLT receptor modulators.<\/jats:p>","DOI":"10.31083\/jin45522","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T11:12:51Z","timestamp":1765019571000},"source":"Crossref","is-referenced-by-count":2,"title":["Effects and Mechanisms of Melatonin Receptor Agonist and Antagonist on Disease Progression in a 6-OHDA-Induced Parkinson\u2019s Disease Rat Model"],"prefix":"10.31083","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8316-8364","authenticated-orcid":true,"given":"Renxi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Fujian Medical University, 350122 Fuzhou, Fujian, China"},{"name":"Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Medical University, 350122 Fuzhou, Fujian, China"},{"name":"Experimental Teaching Center of Basic Medicine, Fujian Medical University, 350122 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Fujian Medical University, 350122 Fuzhou, Fujian, China"},{"name":"Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Medical University, 350122 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Lin","sequence":"additional","affiliation":[{"name":"Experimental Teaching Center of Basic Medicine, Fujian Medical University, 350122 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Fujian Medical University, 350122 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Fujian Medical University, 350122 Fuzhou, Fujian, China"},{"name":"Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 350001 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Fujian Medical University, 350122 Fuzhou, Fujian, China"},{"name":"Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Medical University, 350122 Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Dickson DW. 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