Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.
Biomed Pharmacother. 2017 Aug;92:373-383. doi: 10.1016/j.biopha.2017.05.094. Epub 2017 May 26.
Melatonin is a neurohormone that is linked to the aetiopathogenesis of schizophrenia. The aim of this study was to assess the potentials of oral melatonin supplement in the management of induced schizophrenia-like behavioural and brain oxidative status changes, using an animal model. The relative degrees of modulation of ketamine-induced behaviours by haloperidol, olanzapine or melatonin were assessed in the open-field, Y-maze, elevated plus maze and the social interaction tests. 12-week old, male mice were assigned to six groups of ten each (n=10). They were pretreated with daily intraperitoneal ketamine at 15mg/kg (except vehicle) for 10days, before commencement of 14day treatment with standard drug (haloperidol or olanzapine) or melatonin. Ketamine injection also continued alongside melatonin or standard drugs administration for the duration of treatment. Melatonin, haloperidol and olanzapine were administered by gavage. Treatments were given daily, and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for the estimation of glutathione, nitric oxide and malondialdehyde levels. Ketamine injection increased open-field behaviours; while it decreased working-memory, social-interaction and glutathione activity. Nitric oxide and malondialdehyde levels also increased after ketamine injection. Administration of melatonin was associated with variable degrees of reversal of these effects. In conclusion, melatonin may have the potential of a possible therapeutic agent and/or adjunct in the management of schizophrenia.
褪黑素是一种与精神分裂症发病机制有关的神经激素。本研究旨在评估口服褪黑素补充剂在管理诱导的类似精神分裂症的行为和大脑氧化状态变化方面的潜力，使用动物模型。通过旷场、Y 迷宫、高架十字迷宫和社交互动测试评估了氟哌啶醇、奥氮平或褪黑素对氯胺酮诱导行为的调节程度。将 12 周龄雄性小鼠分为 6 组，每组 10 只（n=10）。它们每天接受 15mg/kg 的腹腔内氯胺酮预处理（除载体外），共 10 天，然后开始用标准药物（氟哌啶醇或奥氮平）或褪黑素进行 14 天治疗。氯胺酮注射也在褪黑素或标准药物给药期间继续进行，持续整个治疗过程。褪黑素、氟哌啶醇和奥氮平通过灌胃给药。每天给药一次，并在第 11 天和第 24 天评估行为。在第 24 天，处死动物并使用全脑匀浆来估计谷胱甘肽、一氧化氮和丙二醛的水平。氯胺酮注射增加了旷场行为；而它降低了工作记忆、社交互动和谷胱甘肽活性。氯胺酮注射后，一氧化氮和丙二醛水平也增加。褪黑素的给药与这些作用的不同程度逆转有关。总之，褪黑素可能具有作为精神分裂症治疗剂和/或辅助治疗的潜力。
