异丙酚诱发大鼠精神依赖性的评价

Assessment of propofol-induced psychic dependence in rats

目的评价异丙酚是否可诱发大鼠精神依赖性。方法清洁级雄性SD大鼠24只，体重240～270g，周龄14周，麻醉下右颈外静脉置管，7d后开始连续14d的自身给药实验。随机分为4组（n=6）：脂肪乳对照组（c组）、异丙酚0．56mg／kg组（P，组）、异丙酚1．00mg／kg组（R组）和异丙酚1．70mg／kg组（B组）。实验由计算机控制，每天限定最高注射次数为50次，P1组、P2组和B组每次分别静脉注射异丙酚0．56、1．00、1．70mg／kg，C组静脉注射脂肪乳0．1ml／kg。记录大鼠每天有效鼻触次数、无效鼻触次数、注射药物次数及最后3d异丙酚日注射量。结果与C组和P1组比较，R组和P1组有效鼻触次数和注射药物次数增加（P〈0．01）；与P，组比较，P1组有效鼻触次数和注射药物次数增加（P〈0．01）。C组与P1组有效鼻触次数和注射药物次数比较差异无统计学意义（P〉0．05）；4组间无效鼻触次数比较差异无统计学意义（P〉0．05）。P1组、P，组和P1组最后3d异丙酚日注射量呈剂量依赖性（P〈0．01）。结论异丙酚诱发大鼠精神依赖性，与其剂量有关。

Objective To assess whether propofol can induce stable psychic dependence in the rats by self-administration experiment. Methods Twenty-four male SD rats 14 weeks old weighing 240-270 mg were studied. Anesthesia was performed with intraperitoneal injection of 3 % sodium pentobarbital 40 mg/kg and atropine 0.3 mg/kg. A catheter was inserted into the right external jugular vein. Penicillin （100 000 U） 0.2 ml was injected through the external jugular vein for anti-infection and heparin sodium （50 U/m]） 0.1 ml for anticoagulation. The self-administration experiment of 14 days was started after the 7 days of recovery. All the rats were randomly divided into 4 groups （ n = 6 each） ： control group （C）, propofol 0.56 mg/kg group （P1）, propofol 1.00 mg/kg group （P2） and propofol 1.70 mg/kg group （P3）. The experimental events were controlled by a computer with 50 times of the maximum injection per day. The times of active and inactive nose-poke response and times of drug injection were recorded per day. Results Compared with group C and P1 , the times of active nosepoke response and injections were significantly increased in group P2 and P3 （ P 〈 0.01 ）. The times of active nosepoke response and injections per day were significantly increased in group P3 than in group P2 （ P 〈 0.01 ） . There was no significant difference in the times of active nose-poke response and injections between group C and P1. There was no significant difference in inactive nose-poke response between the 4 groups. And the total daily doses of propofol injected in the last 3 days were significantly increased in a dose-dependent manner. Conclusion Propofol can induce the development of psychological dependence in rats and it is related to the dosage.