褪黑素对大鼠空间学习记忆的影响及其机制研究 　
　


冯寅1, 张烈雄2, 晁东满3
(1复旦大学医学院神经生物学教研室，上海 200032;
2华东师范大学生命科学学院生理学教研室，上海 200062;
3复旦大学医学院生理学教研室，上海 200032)
　

 　
　

摘 要: 
本研究运用Morris水迷宫和电生理学方法，以逃避潜伏期、穿环系数和海马CA1区突触长时程增强（long-term potentiation, LTP）为指标，研究褪黑素对大鼠空间学习记忆能力的影响。实验结果显示：（1）在Morris水迷宫6 d训练中，对照组大鼠后4 d平均逃避潜伏期为18.44±2.7 s，褪黑素组为30.02±3.6 s，两者有显著差异（P<0.01）；训练６ d后，褪黑素组穿环系数为25.68±2.32%，明显小于对照组的43.33±2.85%（P<0.01）。　（2）采用微量注射法给予海马CA1区褪黑素，强直后60 min，fEPSP斜率为基准值的114.28±1.80%，显著低于对照组的169.71±6.48%（P<0.01）。　（3）  预先给予东莨菪碱，不影响褪黑素对海马CA1区LTP的抑制，强直后60 min fEPSP斜率为基准值的113.70±5.55%。（4）提前给予荷包牡丹碱后给予褪黑素，强直后60 min fEPSP斜率为基准值的162.29±10.52%，明显大于褪黑素组（P<0.01），而与对照组无显著差异（P>0.05）。上述结果表明，褪黑素对大鼠的空间学习记忆能力及海马CA1区LTP均有明显的抑制作用，两者相关；东莨菪碱不能阻断褪黑素对海马CA1区LTP的抑制作用，而荷包牡丹碱可以阻断褪黑素对LTP的抑制，提示褪黑素的作用可能不是由胆碱能系统所介导，而是通过GABA能系统介导。

 关键词:
褪黑素;  空间学习记忆;  长时程增强;  东莨菪碱;  荷包牡丹碱
学科分类号: Q427

 　
　 　 　
　

Role of melatonin in spatial learning and memory in
rats and its mechanism
WU Guo-Ji, CHEN Zheng-Qiu, SHI Hong
(Institute of Acupuncture, China Academy of  Traditional Chinese Medicine,  Beijing 100700)

Abstract:
It has been suggested that melatonin is involved in learning and memory. In the present study, we investigated the effects of melatonin on spatial learning and memory in rats, using Morris water maze and electrophysiological methods.The results are as follows:  (1)  During a six-day water maze training, the mean escape latency of melatonin group in the last 4 days was 30.02±3.6s, and that of control group was 18.44±2.7 s (P<0.01). The crossing annulus coefficient of melatonin group was 25.68±2.32%, and that of control group was 43.33±2.85% (P<0.01).  (2)  Microinjection of melatonin into CA1 area inhibited long-term potentiation (LTP). Sixty  min after tetanus, the field excitory postsynaptic potentials      (fEPSP) slope of group C (n=7，  0.5 μl saline) was 169.71±6.48% of the baseline, and group M2 (n=6, 2 μg melatonin), was 114.28±1.80% of the baseline. The difference is significant (P<0.01).   (3)  We also investigated the effects of melatonin on LTP after administration of scopolamine. Sixty  min after tetanus, the fEPSP slope of group SM (n=6, 2 μg scopolamine before 2  μg melatonin) was 113.70±5.55% of the baseline.  It showed a significant decrease compared with[JP2] group C (P<0.01). However, there was no difference between groups SM and  M2 (P>0.05,  i.v.)  The results   obtained by applying melatonin after bicuculline were different from those after scopolamine.   Sixty min after tetanus, the fEPSP slope of group BM (n=7, 1 μg bicuculline before 2  μg melatonin) was 162.29±10.52% of the baseline. Compared with group C, there is no significant difference (P>0.05); but compared with group M2, the difference is significant (P<0.01). Our results showed that application of melatonin in rats significantly inhibited not only spatial learning and memory, but also LTP in CA1 area. Furthermore, the results indicates that the inhibition of LTP by melatonin may not be mediated by cholinergic system, but may be through the modulation of GABAergic system.

Key words:
melatonin;    spatial   learning and memory;  longterm potentiation;   scopolamine;  bicuculline
　

 　
　 　 　
　

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