小剂量甲基苯丙胺对线索诱导药物复吸行为的影响

Effects of low-dose methamphetamine on cue-induced drug relapse

目的:探讨小剂量甲基苯丙胺(METH)引燃对线索诱导的METH复吸行为的影响。方法:SD大鼠在固定比率(FR=1)程序下进行METH(0. 05 mg·kg^(-1),0. 2 g·L^(-1))自身给药训练,每天4 h,连续14 d,随后置于饲养笼内自然戒断14 d。在戒断的第15 d,大鼠随机分为3组,分别腹腔注射生理盐水、极小剂量METH(0. 025 mg·kg^(-1))和小剂量METH(0. 075 mg·kg^(-1)),进行环境线索(context cue,CC)诱导的大鼠METH复吸测试;在戒断的第16d,大鼠腹腔分别注射相同剂量的生理盐水或METH,随后进行条件性线索(conditioned cues,CS)诱导的大鼠METH复吸测试。结果:大鼠METH自身给药训练14 d后,有效鼻触数和注射针数明显上升并稳定在较高水平,而无效鼻触数一直维持在较低的水平,说明自身给药模型的成功建立。CC诱导大鼠METH复吸测试时,单因素方差分析显示各组的有效鼻触数有显著性差异(F(2,21)=8. 326,P=0. 002)。与对照组比较,小剂量METH组的有效鼻触数极明显升高(P <0. 05),而极小剂量METH组的有效鼻触数无统计学差异(P> 0. 05)。而在CS诱导大鼠METH复吸测试时,单因素方差分析显示各组的有效鼻触数也有显著性差异(F(2,21)=9. 105,P=0. 001)。与对照组相比,小剂量METH组的有效鼻触数明显升高(P <0. 05),而极小剂量METH组的有效鼻触数无统计学差异(P> 0. 05)。CS诱导的有效鼻触反应比CC的诱导作用更强烈。结论:0. 075 mg·kg^(-1)的METH与相关的CC和CS相互作用可以再次恢复大鼠原来的自身给药反应行为。0. 075 mg·kg^(-1)的METH是有效引燃剂量。

training for 4 hours everyday and 14 d.Then all rats were returned to home cage for withdrawal.On the15th day of withdrawal,the rats were randomly divided into 3 groups and were given intraperitoneal injections of saline,very low doses of methamphetamine（0.025 mg·kg^（-1））and low doses of methamphetamine（0.075 mg·kg^（-1））,then were tested methamphetamine seeking behavior induced by context cue（CC）.On the 16th day of withdrawal,rats were given the same dose of saline or methamphetamine intraperitoneally,followed by conditioning cues（CS）induced methamphetamine of all rats increased significantly and stabilized high levels,whereas the number of inactive nose pokes remained at a lower level.One-way analysis of variance showed that there was a significant difference in the active pokes between different doses of methamphetamine groups after CC-induced seeking testing（F（2,21）=8.326,P=0.002）.Compared with saline control group,the active nose pokes of the lowdose（0.075 mg·kg^（-1））METH rats increased significantly（P〈0.05）,but the very low-dose methamphetamine group didn’t（P〈0.05）.One-way analysis of variance also showed that different doses of methamphetamine treatment also had significant differences in the active pokes after CS-induced seeking testing（F（2,21）=9.105,P=0.001）.Compared with saline control group,the active nose pokes of the low-dose（0.075 mg·kg^（-1））METH rats increased significantly（P〈0.05）,but also the very low-dose methamphetamine group didn’t（P〈0.05）.The condition cues-induced METH is the effective priming dose.