褪黑素对吗啡戒断小鼠学习记忆及海马CA1区细胞数的影响

目的　观察褪黑素 (melatonin ,MT)对吗啡戒断小鼠学习记忆能力及海马CA1区细胞数的影响并探讨其机制。方法　建立小鼠吗啡依赖模型 ,皮下注射定量吗啡 ,在注射吗啡的同时每天 2次 (早晚 8:0 0 )用不同剂量的MT(2 .5、5、10mg·kg 1)给小鼠灌胃 ,腹腔注射纳络酮 (5mg·kg-1)催瘾 ,观察其戒断症状 ,电迷宫法检测小鼠学习记忆情况 ;行为学检测结束后 ,处死动物 ,取出全脑 ,固定切片 ,进行形态学观察。结果　褪黑素低、中、高剂量组学习记忆能力与吗啡戒断组比有显著差异 (P <0 .0 5 ,P <0 .0 1,P <0 .0 0 1) ,在该实验剂量范围内有较好的量效关系 ;3组海马CA1区的细胞数与吗啡戒断组比有显著差异 (P <0 .0 5 ,P <0 .0 1,P <0 .0 0 1)。结论　MT对吗啡戒断致小鼠学习记忆障碍有改善作用 ,这种作用可能与褪黑素保护海马CA1区神经细胞有关。

Effects of melatonin on learning and memory activity and number of hippocampal CA1 neurons in mice of morphine withdraw

Objective To observe the effects of melatonin(MT)on learning and memory activity and number of hippocampal CA1 neurons in mice induced by morphine withdraw and explore its mechanism.Method A physical dependent model of morphine in mice was established by subcutaneous injection of morphine.At the same time,MT was administered by intragastric perfusion with three different dose(2.5,5 and10mg·kg -1 ,respectively).Naloxone(5mg·kg -1 ) was administered intra-peritoneally to intensify addiction.The withdrawal syndrome was observed and the learning and memory was tested by the electric mare method.After behavioral test,the animals were sacrificed,the total brain tissues were removed,fixed,sliced,and then morphological observation were performed.Results The infacacy of learning and memory in three groups with different dose of MT were significantly higher than that of morphine withdrawal group( P <0.05, P <0.01and P <0.001,respectively),and a significan relation exiseted between MT dosage and effects in these dosage.The number of cells in hippocampal CA1 neurous in three different dose of MT groups were higher significantly than that of morphine withdraw group ( P <0.05, P <0.01and P <0.001 respectively).Conclusion MT plays a very important role in improving impaired learning and memory capacity induced by morphine withdraw in mice. The effect may be correlated with the protection of MT on hippocampal CA1 neurons.