小剂量纳洛酮对吗啡致大鼠依赖和耐受的影响

Effects of low dose naloxone on morphine-induced tolerance and dependence in rats

目的:探讨小剂量纳洛酮对吗啡致大鼠耐受和依赖的影响。方法:18只SD大鼠随机分为3组(n=6),即吗啡对照组(M组,皮下注射6mg/kg的吗啡),吗啡复合纳洛酮组(MN1组,皮下注射6mg/kg吗啡和100ng/kg纳洛酮;MN2组,皮下注射6mg/kg吗啡和10ng/kg纳洛酮)。注射药物30min进行痛阈测定,并进行8d条件性位置偏爱(CPP)训练,最后一次注药后24h进行CPP测定。结果:与训练前比较,训练后在黑箱内停留的时间显著延长(P<0.01),与M组比较,MN1和MN2组CPP评分显著降低(P<0.01);与前3d比较,M组大鼠痛阈在从第4天开始显著下降(P<0.01),MN1和MN2组痛阈下降值有显著差异。结论:10ng/kg～1μg/kg的纳洛酮能显著抑制应用吗啡后大鼠耐受和依赖的形成。

Objective： To investigate the effects of low dose naloxone on morphine-induced tolerance and dependence in rats. Methods： Eighteen adult male Sprague-Dawley rats were randomly assigned into group M, group MN1, and group MN2 （n =6）. Rats in group M received 6mg/kg of morphine. Rats in groups MN1 and MN2 were given different doses of naloxone （ 100ng/kg, 10ng/kg） with 6mg/kg of morphine. Pain threshold was determined at thirty minutes after subcutaneous injection of morphine or mixture of morphine and naloxone. Training of conditioned place preference （CPP） was carried out from day one to day eight, and CPP was tested after the last 24h training. Results： The stay time in a morphine-paired white compartment was significantly prolonged. Compared with group M,CPP scores for groups MN1 and MN2 were significantly decreased （P 〈 0.01 ）. Compared with the first three days, the pain threshold in group M was significantly decreased up to the last day （P 〈0.01 ）, and the descending pain threshold level in group M was higher than that in groups MN1 and MN2. Conclusion： The dose of naloxone, ranging 10 - 100ng/kg, can restrain the formation of tolerance and dependence induced by chronic morphine administration.