不同消退方法对吗啡诱导的小鼠条件性位置偏爱行为的影响

目的：比较采用不同的消退方法对吗啡诱导条件性位置偏爱（CPP）的消退及随后小剂量药物诱发点燃的影响。方法小鼠采用交替隔日皮下注射吗啡（10 mg/kg）或等容量生理盐水后在伴药箱或非伴药箱训练共8 d，即接受吗啡和生理盐水训练共4个轮次，使小鼠形成CPP。采用不同的消退方法使小鼠CPP熄灭。方案1：自然消退。小鼠吗啡CPP形成后不做任何处理，待21 d后，每隔7 d进行1次测试，观察其消退程度。方案2：测试消退。小鼠吗啡CPP形成第2天起，每日进行1次消退测试观察其消退程度；方案3：训练消退。小鼠吗啡CPP形成第2天起，用生理盐水代替吗啡，小鼠每日分别在伴药箱和非伴药箱完成一轮训练，每训练2轮测试1次，观察其消退程度。待各组完全消退后间隔2～7 d，皮下注射5 mg/kg吗啡对小鼠CPP进行重建测试。结果吗啡处理诱导小鼠出现显著的CPP效应，自然消退组在CPP形成后第28天仍保持CPP行为，第35天CPP效应消失。消退测试6次，训练熄灭4轮均使得CPP效应消退。以上3种方案消退的小鼠均可被5 mg/kg的吗啡点燃。结论吗啡诱导的小鼠CPP模型可维持28 d以上（自然消退），测试及训练消退的方法均可加速其消退，且5 mg/kg吗啡可诱导各组CPP效应的重建。

Effect of different extinction methods on morphine-induced conditioned place preference in mouse

Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference （CPP）. Methods Mouse received morphine（10 mg/kg, sc） or saline （10 mg/kg, sc） injections alternately for 8 days to establish CPP. Different methods were used for extinction. Program 1, withdrawal group. Extinction sessions were conducted 21 days after the CPP test at 7 days interval; Program 2, extinction test group. Extinction sessions were carried out once a day from the second day after the CPP test; Program 3, extinction training group. Extinction sessions began one day after the CPP test. Mice were treated alternately two trials daily, in compartments where they received saline instead of morphine. A test for reinstatement was performed on the 2nd or 7th day after all groups completed extinction by 5 mg/kg morphine-primed. Results Morphine injections induce strong CPP. In withdrawal group, CPP extinguished on the 35th day and maintained for at least 28 days. Six trials extinction tests and 4 trials extinction training caused morphine induced CPP extinction. The three programs mentioned above were all primed by 5mg/kg morphine. Conclusion Morphine induced mouse CPP model can maintain at least 28 days, both extinction test and training can accelerate the extinction of CPP, and reinstatement by 5 mg/kg morphine.