Bagewadi Harish G, Ak Afzal Khan, Shivaramegowda Rekha M
Assistant Professor, Department of Pharmacology, MVJ Medical College & Research Hospital , Bangalore, India .
Professor, Department of Pharmacology, MVJ Medical College & Research Hospital , Bangalore, India .
J Clin Diagn Res. 2015 Aug;9(8):FF01-5. doi: 10.7860/JCDR/2015/13233.6287. Epub 2015 Aug 1.
Due to the adverse effects produced by the present conventional medicines for anxiety disorders, research for newer drugs is still desirable. From the literature it is evident that NMDA receptors play a key role in animal models of anxiety.
The present study is done to evaluate the antianxiety effect of memantine in swiss albino mice.
The experimental study was conducted from November 2014 to January 2015. Animals were divided into four groups. Twelve mice were randomly allotted in each group. Animals in the first group received normal saline as a control 10ml/kg, lorazepam 0.5mg/kg was administered to second group, memantine 3mg/kg as a test drug was given to the third group and memantine 3mg/kg + lorazepam 0.5mg/kg was administered to the fourth group. All the drugs were given for 7 consecutive days by intraperitoneal route.
Results were analyzed by one-way ANOVA followed by Post-hoc Tukey's test. On the 1(st) day, memantine treated group did not show statistical significant anxiolytic effect in both the behavioural paradigms when compared to control group. On the 8(th) day, the animals showed significant decrease p<0.001 in step down latency period in shock free zone (185.4±3.87 Vs 278.3±5.49), significant increase p<0.001 in step down errors (6.8±0.78 Vs 1.4±0.19) and significant increase p<0.001 in total time spent in shock zone (32.1±2.22 Vs 5.6±0.6). In open field test, on 8(th) day the animals treated with memantine when compared to control group, showed significant increase p<0.001 in number of squares crossed (112.7± 2.69 Vs 83.2±2.96), time spent in central square (11.5±1.26 Vs 3.4±0.65), no. of rearings (32.4±2.61 Vs 17±1.81) and significant decrease p<0.001 in freezing time (15.2±1.12 Vs 20.2±2.29). Memantine showed synergistic antianxiety effect when combined with lorazepam.
Memantine showed significant anxiolytic effect in open field and passive avoidance response tests which are commonly used experimental models to assess anxiety states in animals.
由于目前用于治疗焦虑症的传统药物存在不良反应，因此仍需要研发新型药物。从文献中可以明显看出，N-甲基-D-天冬氨酸（NMDA）受体在焦虑症动物模型中起关键作用。
本研究旨在评估美金刚对瑞士白化小鼠的抗焦虑作用。
实验研究于2014年11月至2015年1月进行。将动物分为四组。每组随机分配12只小鼠。第一组动物接受10ml/kg生理盐水作为对照，第二组给予0.5mg/kg劳拉西泮，第三组给予3mg/kg美金刚作为受试药物，第四组给予3mg/kg美金刚+0.5mg/kg劳拉西泮。所有药物均通过腹腔注射连续给药7天。
结果采用单因素方差分析，随后进行事后Tukey检验。在第1天，与对照组相比，美金刚治疗组在两种行为范式中均未显示出统计学上显著的抗焦虑作用。在第8天，动物在无电击区的步下潜伏期显著缩短（185.4±3.87对278.3±5.49，p<0.001），步下错误显著增加（6.8±0.78对1.4±0.19，p<0.001），在电击区花费的总时间显著增加（32.1±2.22对5.6±0.6，p<0.001）。在旷场试验中，与对照组相比，在第8天接受美金刚治疗的动物穿过方格的数量显著增加（112.7±2.69对83.2±2.96，p<0.001），在中央方格花费的时间显著增加（11.5±1.26对3.4±0.65），直立次数显著增加（32.4±2.61对17±1.81），僵住时间显著缩短（15.2±1.12对20.2±2.29，p<0.001）。美金刚与劳拉西泮联合使用时显示出协同抗焦虑作用。
美金刚在旷场试验和被动回避反应试验中显示出显著的抗焦虑作用，这两种试验是评估动物焦虑状态常用的实验模型。
