司来吉兰对甲基苯丙胺引发的情绪相关行为障碍的神经保护作用：经由5-羟色胺和多巴胺受体介导
Neuroprotective Effects of Selegiline Agent Methamphetamine-Prompted Mood-Related Behavior Disorder Mediated Via 5-HT and D Receptors.
作者信息
Gholami Mina, Kaviani Neda, Motaghinejad Majid, Ulloa Luis
机构信息
Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medicine, Qom Branch, Islamic Azad University, Iran.
出版信息
Int J Prev Med. 2023 Jun 22;14:78. doi: 10.4103/ijpvm.ijpvm_42_22. eCollection 2023.
BACKGROUND
Many previous studies demonstrated that methamphetamine (METH) abuses can cause mood-related behavioral changes. Previous studies indicated neuroprotective effects of Selegiline.
METHODS
Seventy male Wistar rats were randomly divided into eight groups (10 rats in each group). Group 1 and Group 2 received normal saline and methamphetamine (10 mg/kg) for 21 days, respectively. Groups 3, 4, and 5 were treated simultaneously with methamphetamine and Selegiline with doses of 10, 15, and 20 mg/kg for 21 days. Groups 6 and 7 are methamphetamine-dependent groups which received 15 mg/kg of Selegiline with haloperidol (as D receptor antagonist) and trazodone (as 5-HT receptor antagonist) for 21 days, respectively. In days 23 and 24, elevated plus maze (EPM) and open-field test (OFT) were conducted to assess motor activity and mood (anxiety and depression) levels.
RESULTS
METH as 10 mg/kg causes reduction of rearing number, ambulation distances, time spent in central square and also number of central square entries in OFT. Also METH administration causes decreases of time spent in open arm and number of open arm entries and increases of time spent in closed arm and number of closed arm entries in EPM. In contrast, Selegiline (of 10, 15, and 20 mg/kg) inhibited behavioral effects of methamphetamine in both OFT and EPM. Also administration of haloperidol and trazodone inhibited these behavioral protective effects of Selegiline and caused decrease of OFT behaviors (rearing number, ambulation distances, time spent in central square, and also number of central square entries) and also caused decreases of spend times in open arm, number of open arm entries, and also increased closed arm time spending and number of entries in closed arm in EPM.
CONCLUSIONS
Current research showed that Selegiline via mediation of D2 and 5-HT receptors inhibits METH-induced neurobehavioral changes, mood-related behavior, and motor activity disturbances.
背景
许多先前的研究表明，甲基苯丙胺（METH）滥用会导致与情绪相关的行为变化。先前的研究表明司来吉兰具有神经保护作用。
方法
将70只雄性Wistar大鼠随机分为八组（每组10只）。第1组和第2组分别给予生理盐水和甲基苯丙胺（10 mg/kg），持续21天。第3组、第4组和第5组同时用甲基苯丙胺和剂量分别为10、15和20 mg/kg的司来吉兰治疗21天。第6组和第7组是甲基苯丙胺依赖组，分别用15 mg/kg司来吉兰与氟哌啶醇（作为D受体拮抗剂）和曲唑酮（作为5-HT受体拮抗剂）治疗21天。在第23天和第24天，进行高架十字迷宫（EPM）和旷场试验（OFT）以评估运动活动以及情绪（焦虑和抑郁）水平。
结果
10 mg/kg的甲基苯丙胺会导致OFT中竖毛次数、行走距离、在中央方格停留的时间以及进入中央方格的次数减少。此外，给予甲基苯丙胺会导致EPM中在开放臂停留的时间和进入开放臂的次数减少，而在封闭臂停留的时间和进入封闭臂的次数增加。相比之下，10、15和20 mg/kg的司来吉兰在OFT和EPM中均抑制了甲基苯丙胺的行为效应。此外，给予氟哌啶醇和曲唑酮会抑制司来吉兰的这些行为保护作用，并导致OFT行为（竖毛次数、行走距离、在中央方格停留的时间以及进入中央方格的次数）减少，还导致EPM中在开放臂停留的时间、进入开放臂的次数减少，以及在封闭臂停留的时间和进入封闭臂的次数增加。
结论
当前研究表明，司来吉兰通过介导D2和5-HT受体抑制甲基苯丙胺诱导的神经行为变化、与情绪相关的行为以及运动活动障碍。
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