Mahmoudi Javad, Farhoudi Mehdi, Talebi Mahnaz, Sabermarouf Babak, Sadigh-Eteghad Saeed
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Pharmacol Rep. 2015 Jun;67(3):478-84. doi: 10.1016/j.pharep.2014.11.005. Epub 2014 Nov 23.
Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice.
Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D1 and D2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups.
Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2mg/kg, ip) and sulpride (50mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1mg/kg, ip), fluoxetine (1mg/kg, ip) and imipramine (0.1mg/kg, ip) and reduced immobility time in TST.
Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D2 receptors) system.
莫达非尼是一种促醒药物，具有广泛的神经学效应。有证据表明它能产生抗抑郁作用。本研究调查了莫达非尼在小鼠悬尾试验（TST）中的抗抑郁效果。
腹腔注射不同剂量的莫达非尼，然后对动物进行TST和/或旷场试验（OFT）。此外，研究了多巴胺能神经传递在莫达非尼抗抑郁作用中的意义。为此，动物预先用氟哌啶醇（非选择性多巴胺受体拮抗剂）或SCH23390和舒必利（分别为多巴胺D1和D2受体拮抗剂）进行预处理，然后通过TST进行评估。在单独的组中还评估了亚有效剂量的莫达非尼与亚治疗剂量的标准抗抑郁药联合使用的可能效果。
与对照组相比，莫达非尼（75毫克/千克，腹腔注射）在TST中产生了抗抑郁作用，而在OFT中的活动没有任何改变。用氟哌啶醇（0.2毫克/千克，腹腔注射）和舒必利（50毫克/千克，腹腔注射）预处理小鼠可阻断莫达非尼（75毫克/千克，腹腔注射）的抗不动作用。我们还发现，给予SCH23390（0.05毫克/千克，皮下注射）不能拮抗莫达非尼的抗抑郁作用。此外，亚有效剂量的莫达非尼（50毫克/千克，腹腔注射）增强了包括安非他酮（1毫克/千克，腹腔注射）、氟西汀（1毫克/千克，腹腔注射）和丙咪嗪（0.1毫克/千克，腹腔注射）在内的标准抗抑郁药的亚有效剂量，并减少了TST中的不动时间。
结果表明，莫达非尼在TST中诱导了抗抑郁特性，这种作用显然是通过与多巴胺能（D2受体）系统相互作用介导的。
