Oliveira Tatiana de Queiroz, de Sousa Caren Nádia Soares, Vasconcelos Germana Silva, de Sousa Luciene Costa, de Oliveira Anneheydi Araújo, Patrocínio Cláudio Felipe Vasconcelos, Medeiros Ingridy da Silva, Honório Júnior José Eduardo Ribeiro, Maes Michael, Macedo Danielle, Vasconcelos Silvânia Maria Mendes
Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
Laboratory of Pharmacology, University Center Christus - Unichristus, Fortaleza, CE, Brazil.
J Affect Disord. 2017 Sep;219:49-57. doi: 10.1016/j.jad.2017.05.022. Epub 2017 May 11.
Depression is accompanied by activated neuro-oxidative and neuro-nitrosative pathways, while targeting these pathways has clinical efficacy in depression. This study aimed to investigate the effects of mirtazapine (MIRT) alone and combined with alpha-lipoic acid (ALA) against corticosterone (CORT) induced behavioral and oxidative alterations.
Male mice received vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days they were divided in groups administered: vehicle, MIRT 3mg/kg or the combinations MIRT+ALA100 or MIRT+ALA200. On the 21st day of treatment, the animals were subjected to behavioral tests. Twenty-four hours after the last drug administration hippocampus (HC) and striatum (ST) were dissected for the determination reduced glutathione (GSH), lipid peroxidation (LP) and nitrite levels.
CORT induced anxiety- and depressive-like behaviors as observed by increased immobility time in the tail suspension test and decreased sucrose consumption. MIRT or MIRT+ALA are effective in reversing anxiety- and depressive-like behaviors induced by CORT. CORT and MIRT alone prolonged sleeping time and this effect was reversed by MIRT+ALA. CORT significantly increased LP, which was reversed by MIRT or MIRT+ALA. Nitrite levels were increased in CORT-treated animals and reversed by MIRT+ALA200 (HC), MIRT or MIRT+ALA (ST).
A relative small sample size and lack of a washout period between drug administration and behavioral testing.
MIRT or MIRT+ALA reverse CORT-induced anxiety- and depressive-like behaviors probably via their central antioxidant effects. Augmentation of MIRT with ALA may reverse sedation, an important side effect of MIRT. Randomized controlled studies are needed to examine the clinical efficacy of this combination in human depression.
抑郁症伴有神经氧化和神经亚硝化途径的激活，而针对这些途径在抑郁症治疗中具有临床疗效。本研究旨在探讨米氮平（MIRT）单独使用及与α-硫辛酸（ALA）联合使用对皮质酮（CORT）诱导的行为和氧化改变的影响。
雄性小鼠在14天内接受溶剂或20mg/kg CORT处理。从第15天到第21天，将它们分为以下几组给药：溶剂、3mg/kg MIRT或MIRT+ALA100或MIRT+ALA200组合。在治疗的第21天，对动物进行行为测试。最后一次给药24小时后，解剖海马体（HC）和纹状体（ST），测定还原型谷胱甘肽（GSH）、脂质过氧化（LP）和亚硝酸盐水平。
通过尾悬测试中不动时间增加和蔗糖消耗减少观察到，CORT诱导了焦虑样和抑郁样行为。MIRT或MIRT+ALA可有效逆转CORT诱导的焦虑样和抑郁样行为。单独使用CORT和MIRT可延长睡眠时间，而MIRT+ALA可逆转这种作用。CORT显著增加LP，MIRT或MIRT+ALA可使其逆转。CORT处理的动物亚硝酸盐水平升高，MIRT+ALA200（HC）、MIRT或MIRT+ALA（ST）可使其逆转。
样本量相对较小，且在给药和行为测试之间缺乏洗脱期。
MIRT或MIRT+ALA可能通过其中心抗氧化作用逆转CORT诱导的焦虑样和抑郁样行为。用ALA增强MIRT可能逆转镇静作用，这是MIRT的一个重要副作用。需要进行随机对照研究来检验这种组合在人类抑郁症中的临床疗效。
