孕晚期吗啡暴露子代鼠NR2B亚基与吗啡条件位置偏爱易感性的关系

Morphine-induced conditioned place preference and alteration of NR2B subunit level in offspring rats undergone late gestational morphine exposure

目的:探讨吗啡条件性位置偏爱(CPP)不同易感性的孕晚期吗啡暴露的子代鼠脑伏隔核(NAc)中N-甲基-D-天冬氨酸(NMDA)受体NR2B亚基水平。方法:孕晚期SD大鼠48只随机分为吗啡组(M组)和生理盐水组(N组)。首剂量为2 mg/kg,逐日递增1 mg/kg,至6 mg/kg维持,头颈部皮下注射。N组孕鼠以同样的方式注射等体积的生理盐水。取上述2组体质量接近的子代鼠各70只,正常喂养至8周龄。每组子代鼠采用恒量法(3 mg/kg)连续颈背部皮下注射吗啡7 d进行条件位置偏爱(CPP)训练,训练结束24 h后对CPP效应进行检测。根据吗啡条件化训练后CPP分值(CPP测试值-CPP基数值)的大小将M组子代鼠分为高偏爱组(n=10)、中偏爱组(n=30)、低偏爱组(n=10)。采用Western blotting方法检测高,低偏爱组和N组子代鼠伏隔核区NR2B亚基的表达。结果:1预测试时,各组的CPP基数值的差异无统计学意义(P>0.05);吗啡高偏爱组CPP分值(552.6±132.6)s明显高于低偏爱组(223.4±55.14)s和N组子代鼠(42.93±31.78)s(P<0.01),差异有统计学意义。2Western blotting结果示高偏爱组子代鼠的NR2B亚基表达量(0.81±0.01)均明显高于低偏爱组(0.64±0.01)和N组子代鼠(0.55±0.01,P<0.01)。结论:产前吗啡暴露的子代鼠吗啡CPP易感性高可能与伏隔核的NR2B亚基水平上调有关。

Objective： To examine the relationship of NR2B subunit expression and susceptibility of morphine-induced conditioned place preference（CPP） in offspring rats undergone late gestational morphine exposure. Methods： Forty-eight late pregnant SD rats were randomized into morphine group （ group M） and saline group （ group N）. Pregnant rats in group M were subcutaneously administered with morphine by initial dose in 2 mg/kg,with daily increment at 1 mg/kg till final 6 mg/kg. Pregnant rats in group N were administered with the same volume of saline as the same protocol. Seventy offspring rats with sim- ilar body weight were selected from the two groups, and conventionally fed for 8 weeks. Constant dose of morphine （3 mg/kg） was subcutaneously adminis- tered at the back of neck for 7 days to start conditioned place preference（CPP） paradigm, and the CPP effects were examined after 24 h of condition. Then the rats were divided into high CPP（ n = 10）, moderate CPP（ n = 30 ） and low CPP group （n = 10 ） on the CPP scores measured. Western blot was per- formed to determined the NR2B expression in offspring rats with high CPP and low CPP. Results：CPP cardinality value at pre-test had no statistical differ- ence for the two groups（ P 〉 0.05 ）, yet the scoring was significantly higher in high CPP（ 552.6 ± 132.6） s group than that of low CPP （ 223.4 ± 55.14 ） s and group N（42.93 ±31.78 ）s. The difference was significant（ P 〈 0.01 ）. Western blotting revealed that high CPP group had higher NR2B expression （0.81 ±0.01 ） over the low CPP（0.64 ±0.01 ） and group N（0.55 ±0.01 ,P 〈0.01 ）. Conclusion ：Higher susceptibility of morphine-induced CPP was found in offspring rats undergone late gestational morphine exposure, suggesting that this vulnerability may be associated with up-regulated NR2B level.