静脉累进比率比较不同剂量丙泊酚的奖赏效应

Comparison of the reward effect of different doses of propofol through intravenous progressive ratio

目的建立丙泊酚静脉自身给药大鼠模型,采用累进比率程序测量丙泊酚的断点并分析不同剂量丙泊酚的奖赏效应。方法清洁级雄性SD大鼠,体重250~280 g,周龄14周,麻醉下右颈内静脉置管,恢复7 d后采用固定比率1∶1程序进行静脉自身给药实验。大鼠对1.70 mg/kg丙泊酚形成稳定的自身给药行为后,选取24只大鼠随机分为3组(每组n=8):丙泊酚0.56 mg/kg组(P1组)、丙泊酚1.00 mg/kg组(P2组)、丙泊酚1.70 mg/kg组(P3组),继续稳定训练5 d,转为PR程序训练5 d。实验由计算机控制,并记录大鼠的有效鼻触次数、无效鼻触次数和药物泵注次数。结果3组大鼠均能建立静脉自身给药行为。3组大鼠最后3 d的平均断点(Breakpiont)分别为P1组:(5.3±1.1)次,P2组:(7.5±1.2)次,P3组:(12.1±1.9)次,差异有统计学意义(P<0.05)。在PR程序训练下,大鼠有效鼻触次数和泵注次数随丙泊酚剂量的增加而明显增加,差异有统计学意义(P<0.01)。结论在一定剂量范围内,丙泊酚的奖赏效应与给药剂量呈正相关。

Objective To establish a rat model of intravenous self-administration of propofol to measure the breakpoint of propofol by progressive ratio program and to analyze the reward effect of different doses of propofol.Methods Male SD rats of clean grade,weighing 250~280 g,aged 14 weeks,received right internal jugular vein catheterization under anathesia.After 7 d of recovery,the intravenous self-administration experiment was carried out with the procedure of a fixed ratio of 1∶1.After the rats formed a stable behavior of self-administration of 1.70 mg/kg propofol,24 rats were selected and randomly divided into 3 groups(for each group,n=8):the propofol 0.56 mg/kg group(group P1),the propofol 1.00 mg/kg group(group P2)and the propofol 1.70 mg/kg group(group P3),which were trained and stabilized for another 5 d and then transferred to PR training lasting for 5 d.The experiment was controlled by computer,and the times of effective nasal contact,ineffective nasal contact and drug pump injection of the rats were recorded.Results All the rats of 3 groups were able to establish their intravenous self-administration behavior.In the last 3 days,the average breakpoints of the three groups were respectively(5.3±1.1)times(group P1),(7.5±1.2)times(group P2)and(12.1±1.9)times(group P3),respectively and the differences were statistically significant(P<0.05).Under the PR training,the times of effective nasal contact and drug pump injection of the rats increased significantly with the increase of the dosage of propofol,and the differences were statistically significant(P<0.01).Conclusion Within a certain dose range,the reward effect of propofol is positively correlated with the dose administered.