The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus
The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus
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DOI：
10.1016/0361-9230(95)02041-1
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发表时间：
1996-01-01
影响因子：
3.8
通讯作者：
Teyler, TJ
中科院分区：
文献类型：
--
作者：
Lee, GYP;Brown, LM;Teyler, TJ
在海马CA 1区，至少存在两种形式的长时程增强（LTP）：一种是N-甲基-D-天冬氨酸（NMDA）受体依赖的LTP（NMDA LTP），其用25 Hz强直刺激诱导并被50 μ M 2-氨基-5-膦酰基戊酸（APV）阻断;另一种是NMDA受体非依赖性LTP（VDCC LTP），其在APV存在下由200 Hz强直刺激诱导并被硝苯地平阻断，电压依赖性Ca++通道（VDCC）阻断剂，或通过细胞内注射1，2-双（2-氨基苯氧基）乙烷-N，N，N ′，N ′-四乙酸（BAPTA）。在大鼠海马脑片上研究了抗惊厥药物苯巴比妥、苯妥英和丙戊酸对NMDA LTP和VDCC LTP的影响。结果表明，0.1mg/ml丙戊酸可使基线群体峰电位幅值改变34.6%，而其他药物对基线群体峰电位幅值无明显影响。苯巴比妥（0.025mg/ml）可有效阻断NMDA LTP，抑制MCC LTP。苯妥英钠（0.02mg/ml）对NMDALTP无影响，但降低VDCCLTP。丙戊酸不抑制VDCC LTP，但以与H-7（一种非特异性蛋白激酶C抑制剂）相似的方式消除NMDA LTP的表达。这些数据表明，这三种药物的抗惊厥作用可能是通过不同的细胞机制。
In hippocampal CA1 area, there are at least two forms of long-term potentiation (LTP): one is N-methyl-D-aspartate (NMDA) receptor-dependent LTP (NMDA LTP), which is induced with a 25 Hz tetanus and blocked by 50 mu M 2-amino-5-phosphonovaleric acid (APV); the other is NMDA receptor-independent LTP (VDCC LTP), which is induced by 200 Hz tetanus stimulation in the presence of APV and blocked by nifedipine, a voltage-dependent Ca++ channel (VDCC) blocker, or by the intracellular injection of 1,2-bis(2-Aminophenoxoy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). The effects of anticonvulsant drugs phenobarbital, phenytoin, and valproic acid on both NMDA LTP and VDCC LTP were investigated in rat hippocampal slices. The results showed that 0.1 mg/ml valproic acid significantly altered baseline population spike amplitude by 34.6%, but the other drugs had no significant effect on the baseline population spike amplitude, Phenobarbital (0.025 mg/ml) potently blocked NMDA LTP and inhibited MCC LTP. Phenytoin (0.02 mg/ml) had no effect on NMDA LTP but reduced VDCC LTP. Valproic acid did not inhibit VDCC LTP, but it abolished the expression of NMDA LTP in a similar manner as H-7, a nonspecific protein kinase C inhibitor. These data suggest that the anticonvulsant effects of these three drugs may be via different cellular mechanisms.