孕晚期吗啡暴露对子代鼠吗啡成瘾易感性的影响

Late gestational morphine exposure increasing addiction vulnerability in offspring rats

目的：检测孕晚期吗啡暴露对子代鼠吗啡成瘾易感性的影响。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）。 M组孕鼠在孕12～18 d每天9∶00和17∶00两次皮下注射吗啡，首剂量为2 mg／kg，逐日递增1 mg／kg，至6 mg／kg维持。 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50只正常喂养至8周龄。每组子代鼠先采用恒量法（吗啡剂量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；之后继续采用递增法（吗啡首剂量4 mg／kg，逐日递增1 mg／kg）以同样方式注射吗啡连续训练7 d至10 mg／kg，训练结束24 h后对子代鼠再次进行CPP效应的检测。结果：①预测试时，两组的CPP基数值[分别为（99．2±22．96） s和（86．1±20．27）s]差异无统计学意义（P＞0．05）；经过7 d的吗啡恒量训练后，M组子代鼠CPP测试值（284．6±58．93）s相对于基线值（99．2±22．96）s明显增高（P＜0．01），而N组子代鼠CPP测试值（116．6±36．95）s与基线值（86．1±20．27）s相比无明显差异（P＞0．05）；继续经过7 d的吗啡递增量训练后，M组和N组子代鼠CPP测试值[分别为（432．3±74．21） s，（221．0±58．26）s]与CPP基线值[分别为（99．2±22．96）s，（86．1±20．27）s]相比均出现差异（P＜0．01，P＜0．01），M组子代鼠CPP测试值（432．3±74．21）s与N组（221．0±58．26）s相比差异有统计学意义（P＜0．05）；且M组子代鼠CPP分值（331．4±69．47）s明显高于N组子代鼠CPP分值（124．8±58．68）s（P＜0．05）。结论：孕晚期吗啡暴露可增加子代鼠对吗啡的成瘾易感性。

Obej ctive： To observe the impact of late pregnancy morphine exposure to addiction vulnerability in offspring of rats .Methods：Forty-eight late pregnant SD rats were randomized divided into morphine group （ M group） and saline group （ N Group） .Pregnant rats in M group were subcutaneously in-jected with morphine at 9：00 AM and 8：00 PM twice daily during 12 to 18 days of pregnancy.Initial dose was 2 mg/kg,and increased at 1 mg/kg day by day till final 6 mg/kg.Pregnant rats in N group were administered with the same volume of saline as the same protocol.Fifty offspring rats with similar body weight were selected from the two groups,and routinely fed for 8 weeks.Constant dose of morphine（3 mg/kg） was subcutaneously administered 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 magnitude dose of morphine（ initial dose at 4 mg/kg by additional 1 mg/kg day by day ） was applied in the same protocol for7 days till final dose of 10 mg/kg,and the CPP effects were further determined after 24 h of conditioning.Results：CPP cardinality value was （99.2 ±22.96）s and （86.1 ±20.27）s for the two groups ,and the difference was not significant（P〉0.05）.After 7 day of constant morphine sensitizing,CPP values were significantly increased in the off-spring rats in group M as compared with baseline values [（284.6 ±58.93）s vs.（ 99.2 ±22.96）s]（P〈0.01）,whereas CPP values remained no signifi-cant difference in group N[（116.6 ±36.95）s vs.（861.±20 .27） s]（P〉0.05）.After magnitude dose conditioning with morphine for 7 days,CPP val-ues tested in the group M and group N were different from the baseline values[（432.3 ±74.21）s and （221.0 ±58.26）s vs.（99.2 ±22.96）s and （86. 1 ±20.27）s]（P〈0.01;P〈0.05）,and group M had significantly higher CPP test values than group N[（432.3 ±74.21）s vs.（221.0 ±58.26）s]（P 〈0.05）.CPP score of group M was significantly higher than group N[（331.4 ±69.47）s vs.（124.8 ±58.68）s]（P〈0.05）.Conclusion：Late gesta-tional morphine exposure may increase the vulnerability of offspring rats to addiction to morphine .