{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:02:33Z","timestamp":1792404153396,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["178075"],"award-info":[{"award-number":["178075"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melatonin is synthesized by the pineal gland with a circadian rhythm in synchrony with the environmental light\/dark cycle. A gradual increase in circulating levels of melatonin occur after lights off, reaching its maximum around the middle of the dark phase. Agonists of melatonin receptors have proved effectiveness as antidepressants in clinical trials. However, there is contradictory evidence about the potential antidepressant effect of melatonin itself. Herein we studied melatonin administration in mice at two zeitgeber times (ZT; ZT = 0 lights on; 12:12 L\/D), one hour before the beginning (ZT11) and at the middle (ZT18) of the dark phase after either a single or a three-dose protocol. Behavioral despair was assessed through a forced-swimming test (FST) or a tail suspension test (TST), at ZT18.5. A single dose of 4 mg\/kg melatonin at ZT11 was effective to reduce the immobility time in both tests. However, acute administration of melatonin at ZT18 was not effective in mice subjected to FST, and a higher dose (16 mg\/kg) was required to reduce immobility time in the TST. A three-dose administration protocol of 16 mg\/kg melatonin (ZT18, ZT11, and ZT18) significantly reduced immobility time in FST. Data indicate that the timely administration of melatonin could improve its antidepressant-like effect.<\/jats:p>","DOI":"10.3390\/ijms19082278","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T11:03:26Z","timestamp":1533294206000},"page":"2278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Timing of Melatonin Administration Is Crucial for Its Antidepressant-Like Effect in Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Rosa","family":"Estrada-Reyes","sequence":"first","affiliation":[{"name":"Laboratorio de Fitofarmacolog\u00eda, Direcci\u00f3n de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Vald\u00e9s-Tovar","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9466-1907","authenticated-orcid":false,"given":"Daniel","family":"Arrieta-Baez","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional CNMN Luis Enrique Erro s\/n Unidad Profesional Adolfo L\u00f3pez Mateos, Gustavo A. Madero, Ciudad de M\u00e9xico 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"Dorantes-Barr\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Fitofarmacolog\u00eda, Direcci\u00f3n de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Quero-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-6931","authenticated-orcid":false,"given":"H\u00e9ctor","family":"Sol\u00eds-Chagoy\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Argueta","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita L.","family":"Dubocovich","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), 955 Main Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-6851","authenticated-orcid":false,"given":"Gloria","family":"Ben\u00edtez-King","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/BF01923947","article-title":"The melatonin rhythm: Both a clock and a calendar","volume":"49","author":"Reiter","year":"1993","journal-title":"Experientia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1210\/jcem-42-4-752","article-title":"Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: Attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs","volume":"42","author":"Vaughan","year":"1976","journal-title":"J. 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