{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:47:18Z","timestamp":1785764838331,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Research Council of T\u00fcrkiye","award":["223S921"],"award-info":[{"award-number":["223S921"]}]},{"award":["223S921"],"award-info":[{"award-number":["223S921"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Melatonin has chronobiotic, antioxidant, anti-inflammatory, and neuromodulatory properties, and its oral effects may vary according to formulation. This study compared conventional melatonin with a lipid-multiparticulate (LMP) formulation in two acute pharmacological mouse paradigms. Eighty-four male BALB\/c mice were assigned to caffeine-evoked cortical activity or pentobarbital-induced sedative-hypnotic experiments. Mice received caffeine (7.5 mg\/kg, i.p.) alone or with standard or LMP-melatonin (10 or 20 mg\/kg, oral). ECoG recorded cortical electrical activity under urethane anaesthesia. In a separate cohort, latency to and duration of pentobarbital-induced loss of the righting reflex were measured. Circulating neurochemical and redox markers, as well as neurotransmitter- and inflammation-related gene and protein expression, were evaluated. Caffeine increased spike frequency and altered ECoG amplitude, together with unfavorable changes in circulating neurochemical and redox markers and in neurotransmitter receptor- and inflammation-related outcomes. Both melatonin formulations attenuated several of these changes in a dose-dependent manner, with the strongest effects generally observed in the high-dose LMP-melatonin group. Compared with conventional melatonin, LMP-melatonin produced greater modulation of ECoG activity, circulating biochemical markers, neurotransmitter-receptor expression, and IL-6 and TNF-\u03b1-related outcomes. LMP-melatonin also produced a greater reduction in the latency to and a greater prolongation of the duration of pentobarbital-induced loss of the righting reflex. LMP-melatonin produced greater formulation-dependent effects than conventional melatonin on caffeine-evoked cortical electrical activity, pentobarbital-induced sedative-hypnotic responses, and selected biochemical and molecular outcomes. However, pharmacokinetic exposure, physiological sleep stages, sleep architecture, sleep quality, and direct measures of neuronal injury were not assessed. Therefore, the findings do not directly establish enhanced bioavailability, physiological sleep promotion, or neuroprotection.<\/jats:p>","DOI":"10.3390\/ijms27156906","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Melatonin Formulations on Caffeine-Evoked Cortical Activity and Pentobarbital-Induced Sleep in Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-1154","authenticated-orcid":false,"given":"Nurhan","family":"Sahin","sequence":"first","affiliation":[{"name":"Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Yabas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Malatya Turgut Ozal University, Malatya 44210, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9583-2218","authenticated-orcid":false,"given":"Besir","family":"Er","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-7253","authenticated-orcid":false,"given":"Fusun","family":"Erten","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Pertek Sakine Gen\u00e7 Vocational School, Munzur University, Tunceli 62500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oznur Ece Durmaz","family":"Kursun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail Gurkan","family":"Cikim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras 46040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4514-2902","authenticated-orcid":false,"given":"Berkan","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Servet Unsal Medical Center, Ankara 06200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2734-7303","authenticated-orcid":false,"given":"Gozde","family":"Erek","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-6215","authenticated-orcid":false,"given":"Busra","family":"Ozmen","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-7689","authenticated-orcid":false,"given":"Cemal","family":"Orhan","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertugrul","family":"Kilic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul 34700, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-5244","authenticated-orcid":false,"given":"Kazim","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13052","DOI":"10.1111\/jsr.13052","article-title":"Dealing with Sleep Problems during Home Confinement Due to the COVID-19 Outbreak: Practical Recommendations from a Task Force of the European CBT-I Academy","volume":"29","author":"Altena","year":"2020","journal-title":"J. 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