大鼠吗啡依赖戒断后焦虑模型的建立和评价

ESTABLISHMENT AND EVALUATION ON ANXIETY MODEL OF MORPHINE-WITHDRAWAL RATS

目的:利用高架十字迷宫建立大鼠吗啡戒断后焦虑模型。方法:342只大鼠按给药总时间的不同,随机分为7、10、14d3大组。每大组各114只,按戒断时间的不同再分设戒断0、24、48、72、96、120、144h、丁螺环酮治疗、生理盐水对照共9小组。采用剂量递增法给药,建立吗啡依赖模型后自然戒断,用高架十字迷宫观察各组大鼠焦虑行为。结果:(1)7d大组,戒断后48h表现出焦虑症状,与生理盐水组比较,其OE、OT、OE%、OT%4项指标均下降(P<0.05)。(2)10d大组,与生理盐水组比较,戒断后48、72、96h均表现出焦虑症状(P<0.05),其中又以72h组最为显著,OE、OT、OE%均明显下降(P<0.01);丁螺环酮治疗组与戒断72h组比较,其OE、OT、OT%均增高(P<0.05),OE%显著增高(P<0.01)。(3)14d给药组,与10d给药组相类似,典型的焦虑症状也出现在戒断后72h,与生理盐水组比较,OE、OT、OT%均明显降低(P<0.01),OE%降低(P<0.05);丁螺环酮组与戒断72h组比较,OE%、OT、OT%均明显增高(P<0.01),OE增高(P<0.05)。结论:吗啡持续给药7、10、14d大鼠通过自然戒断均能成功建立吗啡戒断后焦虑模型,但以10d、戒断72h为最佳。该模型可较为客观和准确地反映吗啡依赖戒断后焦虑行为。

Objective：To establish an anxious model of morphine -withdrawal in rats, based on the elevated plus -maze test. Methods ：Three hundred and forty two SD rats were randomly divided into three groups according to the time of morphine administration： 7 d group, 10 d group and 14 d group. Each group was composed of 9 units, based on morphine - withdrawing time （Tx） where x = 0, 24, 48, 72, 96, 120 and 144 h. In addition, buspirone unit and normal sodium unit were involved. Gradually increasing dosage was used to establish the model of morphine - dependence before anxious model was set up. Anxiety of each group was observed, using elevated plus - maze test. Results ： （ 1 ） The 7 d morphine - administrated group appeared anxious at 48 hours of morphine withdrawal, with the parameters of OE, OT, OE% and OT% decreased compared with the NS control unit（P 〈0. 05）. （2） Anxiety was showed in the morphine - withdrawal units of 48, 72 and 96 h in 10 d morphine -administered group （P 〈0. 05）. Notably, at 72 - hour - withdrawal unit, the parameters of OE, OT and OE% were decreased （ P 〈 0. 01 ）. In buspirone unit, the parameters of OE, OT and OT% were increased （P 〈 0. 05）, and OE% was notably higher than that of 72 - hour - withdrawal unit （ P 〈 0. 01 ）. （ 3 ） The same trend was found between 10 d withdrawal units and 14 d withdrawal units, as described above. Compared with the NS control unit, the parameters of OE, OT and OT% were notably decreased （P 〈 0. 01 ）, and OE% was decreased （ P 〈 0. 05 ）. OE, OT and OT% tended to a distinguished increase in buspirone unit （P 〈 0. 01 ） , though OE% was slightly higher than that of 72 - hour - withdrawal unit （ P 〈 0. 05）. Conclusion： Addictive and anxious model could be appraised by establishing 7 d, 10 d and 14 d morphine - withdrawal group. Howerer, anxious behavior of 10 -day- withdrawal model; more accurate and credible.