胍丁胺联合育亨宾对吗啡诱发小鼠行为敏化的影响

发布时间：2018-05-20 20:29

本文选题：胍丁胺 + 育亨宾　；参考：《国际药学研究杂志》2015年04期

【摘要】：目的研究胍丁胺单独给药及联合α2-肾上腺素受体特异性拮抗剂育亨宾用药对吗啡致小鼠行为敏化的影响。方法1.观察药物处理对小鼠基础活动性的影响。将雄性C57BL/6J小鼠分为盐水对照组、胍丁胺(1、10、20、40和80 mg/kg)组、育亨宾(0.3、1、2和8 mg/kg)组和育亨宾(2 mg/kg)+胍丁胺(80 mg/kg)组,给予胍丁胺(sc)或育亨宾(ip)后测试小鼠60 min的水平移动距离;2.观察药物处理对吗啡诱发小鼠高活动性的影响。小鼠分为盐水对照组、吗啡(10 mg/kg)组、胍丁胺(1、20和80mg/kg)+吗啡(10 mg/kg)组、育亨宾(2 mg/kg)+吗啡(10 mg/kg)组和育亨宾(2 mg/kg)+胍丁胺(80 mg/kg)+吗啡(10 mg/kg)组,单独给予胍丁胺(sc)或育亨宾(ip)以及两药联合使用后给予吗啡(sc),测试药物处理后小鼠60 min的移动距离;3.观察药物处理对吗啡诱发小鼠行为敏化精神依赖行为的影响。采用连续间断给药方式建立敏化模型,在预适应分组后分别在第1天、第4天和第7天给予吗啡(10 mg/kg),同时检测小鼠60 min的移动距离。实验设计中分为盐水对照组、吗啡(10 mg/kg)组、胍丁胺(1、20和80 mg/kg)+吗啡(10 mg/kg)组和育亨宾(2 mg/kg)+胍丁胺(80 mg/kg)+吗啡(10 mg/kg)组,单独给予胍丁胺(sc)或联合育亨宾(ip)用药后给予吗啡(sc),并在给药当天测试小鼠60 min的移动距离,比较给药组与吗啡模型组的差异。结果 1.单独给予胍丁胺(1~80 mg/kg)或育亨宾(0.3~2 mg/kg)的系列剂量后,与盐水对照组比较,小鼠的移动距离无明显差异;2.急性吗啡诱发高活性实验中,伴随给予胍丁胺(1~80 mg/kg)或育亨宾(2 mg/kg)后,与吗啡组比较,小鼠的移动距离均无明显差异,而胍丁胺(80 mg/kg)与育亨宾(2 mg/kg)联合用药后小鼠的移动距离为(22 581.6±11 694.0)cm,显著低于吗啡组(37 577.9±9 657.4)cm(P0.05);3.在吗啡诱导小鼠行为敏化模型中,伴随给予胍丁胺(1~80 mg/kg),其测试当天的移动距离与吗啡模型组比较均无明显差异;当胍丁胺(80 mg/kg)与育亨宾(2 mg/kg)联合用药后小鼠在敏化实验第1天、第4天和第7天的移动距离分别为(21 112.7±5 586.7)cm、(37 672.7±10 518.8)cm和(47 681.0±15 845.3)cm,均显著低于吗啡组(31 156.4±8 010.5)cm(P0.01)、(51 724.9±11 364.51)cm(P0.05)和(63 572.2±12 151.2)cm(P0.05),提示胍丁胺和育亨宾联合用药显著抑制吗啡诱导小鼠行为敏化的形成。结论在C57BL/6J小鼠中,胍丁胺与α2-肾上腺素受体拮抗剂育亨宾联合应用具有抗吗啡行为敏化的作用,为吗啡精神依赖的治疗提供可能的新策略。
[Abstract]:Objective to study the effects of agmatine alone and yohimbine, a specific antagonist of 伪 2 adrenergic receptor, on behavioral sensitization induced by morphine in mice. Method 1. To observe the effect of drug treatment on basic activity in mice. Male C57BL/6J mice were divided into three groups: saline control group, agmatine (10) 20 (40 and 80 mg / kg) groups, yohimbine (0.3 mg / kg and 8 mg / kg) groups and yohimbine (2 mg / kg) agmatine (80 mg / kg) groups. After administration of agmatine (scc) or yohimbine (IP), the horizontal moving distances of 60 min were measured. To observe the effect of drug treatment on morphine induced hyperactivity in mice. Mice were divided into saline control group, morphine 10 mg / kg group, agmatine (20 and 80 mg / kg) morphine 10 mg / kg) group, yohimbine 2 mg / kg morphine 10 mg / kg group and yohimbine 2 mg / kg) agmatine 80 mg / kg) morphine 10 mg / kg group. The mice were given agmatine (scl) or yohimbine (IP) alone and the combination of the two drugs. The mobile distance of the mice after 60 min treatment was measured. To observe the effect of drug treatment on behavioral sensitized psychological dependence behavior induced by morphine in mice. The sensitized model was established by continuous intermittent administration. After preconditioning, 10 mg / kg of morphine was given on day 1, day 4 and day 7, respectively. At the same time, the moving distance of 60 min was measured. The design was divided into three groups: saline control group, morphine 10 mg / kg group, agmatine 20 and 80 mg / kg) morphine 10 mg / kg group and yohimbine 2 mg / kg) agmatine 80 mg / kg) morphine 10 mg / kg group. After administration of agmatine alone or in combination with yohimbine (IP), morphine was given to mice for 60 min, and the difference between the administration group and the morphine model group was compared. Result 1. After a series of doses of 80 mg / kg of agmatine alone or 0.3 mg / kg of yohimbine, there was no significant difference in the distance of movement between the two groups compared with the saline control group. In the acute morphine induced high activity test, there was no significant difference in the movement distance between the two groups after administration of agmatine (80 mg / kg) or yohimbine (2 mg / kg). The mobile distance of mice treated with 80 mg / kg of agmatine and 2 mg / kg of yohimbine was 22 581.6 卤11 694.0 cm, which was significantly lower than that of morphine group (37 577.9 卤9 657.4 cm / kg). In the behavioral sensitization model of mice induced by morphine, the moving distance of agmatine was not significantly different from that of morphine model group on the same day as that of morphine model group, and the mice were treated with agmatine (80 mg / kg) and yohimbine (2 mg / kg) on the first day of sensitization test. The moving distances were 21 112.7 卤5 586.7 518.8)cm and 47 681.0 卤15 845.3 518.8)cm on day 4 and 7, respectively, which were significantly lower than those in morphine group (31 156.4 卤8 010.5 cm, P 0. 01 724.9 卤11 364.51 cm P 0 05) and 63 572.2 卤12 151.2 cm P 0 05, respectively, indicating that agmatine combined with Hengbin significantly inhibited the formation of behavioral sensitization induced by morphine in mice. Conclusion in C57BL/6J mice, the combination of agmatine and 伪 2-adrenoceptor antagonist yohimbine has the effect of anti-behavioral sensitization of morphine, and may provide a new strategy for the treatment of morphine dependence.
【作者单位】：抗毒药物与毒理学国家重点实验室神经精神药理学北京市重点实验室军事医学科学院毒物药物研究所新药评价研究室;
【基金】：国家重点基础研究发展计划(973计划)资助项目(2015CB553504) 国家自然科学基金青年科学基金资助项目(81102426)
【分类号】：R965

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