The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus.
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 microM 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 VDCC 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 anti-convulsant effects of these three drugs may be via different cellular mechanisms.
Lee
G Y
GY
Department of Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095, USA. YPL@UHURA.NEOUCOM.EDU
Brown
L M
LM
Teyler
T J
TJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D013569:Synapses / Q000187:drug effects
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007546:Isoquinolines; D010879:Piperazines; D016202:N-Methylaspartate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C