STUDY OF LONG TERM POTENTIATION (LTP) INDUCED IN VARIOUS BRAIN REGION AND ESTABLISHMENT OF NEW EVALUATION SYSTEM FOR NOOTROPIC DRUGS

我们研究了大脑各区域的长时程增强（LTP）和神经元可塑性，并阐明了以下几点。(1) LTP在大鼠视交叉上核（SCN）诱导，且诱导具有时间依赖性。甲钴胺有助于大鼠SCN LTP的诱导。(2)大鼠SCN的可塑性随年龄增长而降低。(3)众所周知，长期抑郁是由纹状体诱发的。而乙醇戒断可诱导纹状体LTP。NMDA受体和多巴胺能受体参与了纹状体LTP的诱导。(4) NO合酶抑制剂对缺氧/低血糖诱导的大鼠海马CA1突触前尖峰降低具有保护作用。戒酒可增强缺氧/低血糖对2-脱氧葡萄糖摄取的减少，但钙通道阻滞剂和谷胱甘肽可保护这种减少。此外，Ca通道和sigma受体参与了大鼠海马缺氧/低血糖诱导的损伤。(5)纹状体多巴胺能神经末梢的NMDA受体对KCL或谷氨酸能药物的应答效果产生长期变化。代谢性谷氨酸受体可能参与甲基苯丙胺（MAP）诱导致敏的表达。因此，NO的产生在map诱导的行为致敏和多巴胺释放增强的表达中起作用。(6)同时阻断海马代谢性谷氨酸和NMDA受体会破坏大鼠的工作记忆。b-肾上腺素能功能障碍加重海马NMDA受体阻断诱导的大鼠工作记忆损伤。如上所述，我们首先发现LTP在SCN和纹状体中被诱导。这些结果表明，神经元在大脑的各个区域具有可塑性。由于痴呆症的确切机制尚不清楚，因此需要各种评估体系来开发新的有效的益智药物。因此，本研究对益智新药的评价具有一定的指导意义。

We studied long term potentiation (LTP) and neuronal plasticity in various brain regions, and clarified following points.(1) LTP is induced in rat suprachiasmatic nucleus (SCN), and the induction is time-dependent. Methylcobalamin helps the induction of LTP in rat SCN.(2) According to aging, the plasiticity reduces in rat SCN.(3) It is well known that long term depression is induced in the striatum. However, ethanol abstinence induces LTP in rat striatum. NMDA receptors and dopaminergic receptors are involved in the induction of LTP in rat striatum.(4) NO synthase inhibitors protects against hypoxia/hypoglycemia-induced decrease in CA1 presynaptic spikes in rat hippocampal slices. Ethanol abstinence potentiates hypoxia/hypoglycemic decrease in 2-deoxy-glucose uptake, but Ca channel blockers and glutathione protects the decrease. Moreover, Ca channel and sigma-receptors are involved in the hypoxia/hypoglycemica-induced impairment in rat hippocampus.(5) NMDA receptors on dopaminergic nerve terminals in the striatum produces the long-term changes in efficacy of the response to KCL or glutamatergic agents. Metabotropic glutamate receptors may be involved in the expression of metamphetamine (MAP) -induced sensitization. Then, NO production plays a role in the expression of MAP-induced behavioral sensitization and enhancement of dopamine release.(6) Concurrent blockade of hippocampal metabotropic glutamate and NMDA receptors disrupts working memory in the rat. b-adrenergic dysfunction exacerbates impairment of working memory induced by hippocampal NMDA receptor blockade in rats.As described above, we first found that the LTP is induced in the SCN and the striatum. These results suggest that the neurons have the plasticity in various brain regions.Because the precise mechanism is not well-known in dementia, various evaluation system is necessary to produce new effective nootropic drugs. Therefore, our study should be helpful for the evaluation of new nootropic drugs.