孕晚期吗啡暴露对子代大鼠伏隔核NR2B表达的影响

Effect of morphine exposure in late pregnancy on expression of NR2B in nucleus accumbens of off-spring rats

目的 评价孕晚期吗啡暴露对子代大鼠伏隔核含2B亚基的N-甲基-D-天冬氨酸（NM-DA）受体（NR2B）表达的影响.方法 孕14 d的SD大鼠48只,16～ 20周龄,体重400 ～ 600 g,采用随机数字表法分为2组（n=24）：对照组（C组）和吗啡组（M组）.M组于皮下注射吗啡,2次/d（9：00 am和5：00 pm）,首日剂量为2 mg/kg,逐日递增1 mg/kg,至6 mg/kg后每天不再增加剂量直至孕鼠分娩.C组用生理盐水替代吗啡.每组取体重接近的子代大鼠50只,正常喂养至8周龄.每组取30只子代大鼠,采用恒量法连续皮下注射吗啡（3 mg/kg）7 d进行条件性位置偏爱训练,训练结束24 h时,记录伴药区停留时间.每组取10只子代大鼠,分别采用免疫组化法和Western blot法测定伏隔核NR2B的表达水平.结果 与M组比较,C组子代大鼠伴药区停留时间延长,伏隔核NR2B表达上调（P＜0.05）.结论 孕晚期吗啡暴露导致子代大鼠吗啡成瘾易感性的机制与上调伏隔核NR2B的表达有关.

Objective To evaluate the effect of morphine exposure in the late pregnancy on the expression of 2B subunit-containing N-methyl-D-aspartate receptor （NR2B） in the nucleus accumbens of offspring rats.Methods Forty-eight Sprague-Dawley rats at 14 days of gestation,aged 16-20 weeks,weighing 400-600 g,were equally and randomly divided into control group （group C） and morphine group （group M）.In group M,morphine was administered subcutaneously twice a day （9：00 a.m.and 5：00 p.m.） in the initial dose of 2 mg/kg followed by daily increment of 1 mg/kg until 6 mg/kg.The equal volume of normal saline was given instead of morphine in group C.Fifty offspring rats with similar body weight were selected from the two groups,and conventionally fed for 8 weeks.Thirty offspring rats were further selected,morphine 3 mg/kg was injected subcutaneously for 7 consecutive days,and then the rats underwent the conditioned place preference test to monitor the effect.The time spent in drug-paired side （gray area） was recorded at 24 h after the test.Ten offspring rats selected were sacrificed after the test,and the brain was removed.The nucleus accumbens was isolated for detection of the expression of NR2B by immunohistochemistry and Western blot.Results Compared with group M,the time spent in drug-paired side （gray area） was significantly prolonged,and the expression of NR2B in the nucleus accumbens was up-regulated in group C （P〈0.05）.Conclusion The mechanism by which morphine exposure in the late pregnancy causes susceptibility to morphine addiction is associated with up-regulation of NR2B expression in the nucleus accumbens of offspring rats.