甲基苯丙胺诱导小鼠行为敏化模型的构建与评估

目的:探讨不同剂量水平甲基苯丙胺(MA)所诱导的小鼠行为敏化模型的构建与评估方法。方法:40只C57BL/6J小鼠,随机分为5组:生理盐水对照组(NS)和0.5、2、5、10mg·kg-1MA剂量组,各组在形成期连续5d每天腹腔注射(ip)不同剂量药物并记录自主活动情况,转化期停药观察2d后,在d8表达期给予最后一次等量剂量MA,并记录自主活动情况。结果:(1)不同剂量MA作用于实验小鼠,在小剂量水平即能够诱导出明显的行为敏化现象,且随着药物浓度增大,呈现剂量依赖性变化;(2)在10mg·kg-1大剂量水平,小鼠表现为明显的刻板行为,在表达期同样出现了刻板行为的增强现象。结论:本实验为不同剂量的小鼠MA敏化模型提供了比较标准的构建和评估方法;2mg·kg-1MA作用于实验小鼠,诱导出了明显的行为敏化现象,同时其他精神运动改变如刻板行为出现较少,是构建药物依赖行为敏化模型较理想的剂量;利用该行为敏化模型可进一步分析和评估药物依赖治疗性药物的疗效。

CONSTRUCTION AND EVALUATION OF BEHAVIORAL SENSITIZATION MODEL IN METHAMPHETAMINE-INDUCED MICE

Objective:To explorer the construction and evaluation of dose-dependent behavioral sensitization model induced by methamphetamine(MA)in mice. Methods:Forty C57BL/6J mice were randomly divided into five groups:NS control group and MA(0.5,2,5,10 mg·kg-1)group. Mice were treated(ip)with saline or MA(0.5,2,5,10 mg·kg-1)once per day for 5 d and then drug manipulation was suspended for 2 d. On d8,a challenge dose of MA was given and then the locomotor activity was measured. Results:Single dose induced robust behavioral change in C57 mice as evidenced by significantly higher locomotion. Repeated administration of 0.5,2,5,10 mg·kg-1,MA dose-dependently induced behavioral sensitization of mice. Mice given a high dose of MA(10 mg·kg-1)showed stereotyped behavior,which was also on the increase in expression stage. Conclusion:This study provides a standard way to construct and evaluate MA-induced behavioral sensitization model in mice. Mice received 2 mg·kg-1 MA showed significantly higher locomotion but less emotion reactivity such as stereotyped behavior. For that reason,2 mg·kg-1 is an ideal dose for behavioral sensitization model construction. This model can be used to analyze and evaluate healing effect in drug addiction.