纳洛酮与加兰他敏对东莨菪碱所致大鼠空间工作记忆障碍作用的神经机制

Neuromechanism research of naloxone compared with galanthamine on scopolamine-induced impairment of spatial working memory in rats

目的比较纳洛酮与加兰他敏对东莨菪碱所致大鼠空间工作记忆障碍的作用,并对其作用机制进行探讨。方法28只18月龄SD大鼠随机分为正常组、东莨菪碱组、纳洛酮治疗组和加兰他敏治疗组,每组7只。采用Morris水迷宫延缓性匹配任务试验记录每只大鼠前后两次逃避潜伏期的时间。利用免疫组化及图像分析技术定量测定各组大鼠海马和前额叶皮层胆碱乙酰转移酶(ChAT)合成情况,利用电子显微镜技术观察大鼠海马CA1区超微结构的改变。结果前后两次逃避潜伏期在正常组差异呈极显著性(P=0.00),东莨菪碱组无差异,纳洛酮治疗组差异呈显著性(P=0.02),加兰他敏组无差异。各组大鼠海马CA1、CA3区,前额叶皮层神经元ChAT量无差别。纳洛酮和加兰他敏对东莨菪碱大鼠CA1区神经元突触超微结构的影响明显不同,纳洛酮治疗组突触囊泡向突触前膜聚集,大小均一而稀疏,突触后致密物质(PSD)均匀,边界整齐清楚;加兰他敏治疗组突触囊泡大小欠均一,分布弥散,无明显突触前膜聚集现象,PSD欠均匀,边界欠清晰。结论纳洛酮改善障碍空间工作记忆的作用可能与其促进神经元突触囊泡神经递质乙酰胆碱向突触间隙大量释放及增加PSD密度有关。

Objective To explore the effects of naloxone and galanthamine on scopolamine-induced impairment of spatial working memory of rats, and its action neuromechanism. Methods All naive rats were divided at random into normal, scopolamine, naloxone and galanthamine groups. The escape lateneies were recorded in a delayed-matching-to sample variant task in Morris water maze. The expression level of ChAT in area of hippocampus and prefrontal lobe were assayed quantitatively by immunohistochemistry and the computerized image technique. The uhrastructure formation of synaptic plasticity in hippocampus CA1 was observed under electron-microscope. Results The mean escape latencies of two trials were significantly different in normal （t =7.32, P=0. 00） and naloxone （t =3.19, P =0. 02） groups, but not in scopolamine （t = 1.01, P = 0. 35 ） and galanthamine （t = 1.65, P = 0. 15 ） groups. The quantity of ChAT in above areas in four groups was not different statistically （P 〉 0. 05 ）. However, the synaptic plasticity alteration was obviously different in hippocampal CA1 area compared naloxone group （synaptic vesicle gathered to presynaptic membrane, bulk uniform and rarefaction, well-distributed postsynaptic dense （PSD） material with clear boundary] with galanthamine group （without bulk uniform synaptic vesicle, distributed dispertion, had no obvious presynaptie membrane aggregation, no well-distributed PSD, no clear boundary）. Conclus｜ons The effects of naloxone are much better than that of galanthamine in improving scopolamine-induced impairment of spatial working memory in Morris water maze in rats. The action neuromeehanism of naloxone might be due to its enhancing synaptie vesicles exoeytosis and altering synaptic plasticity other than increasing chAT expression in neurons.