The NMDA antagonist, MK-801, suppresses long-term potentiation, kindling, and kindling-induced potentiation in the perforant path of the unanesthetized rat.
Antagonism of NMDA-mediated transmission by MK-801 has been shown to block long-term potentiation (LTP) in vitro and delay electrical kindling of the amygdala. The present experiment sought to examine the relationship between synaptic potentiation of the perforant path-granule cell synapse and development of perforant path kindling. MK-801 (0.1 and 1.0 mg/kg) blocked induction of LTP of the perforant path in the unanesthetized animal measured 24 h after train delivery. The 1.0 mg/kg dosage also increased afterdischarge (AD) thresholds, delayed kindling development from daily stimulation of the perforant path (means = 8.82 +/- 1.19 and 22.9 +/- 3.66 sessions to the first stage 5 seizure), and increased AD durations. Kindling produced a significant potentiation of the EPSP (47%) and population spike (49%) after the first evoked AD in control animals. No significant enhancement of either component of the field potential was observed in MK-801-treated animals. Animals treated with this dosage of MK-801, did, however, kindle in the absence of potentiation at this synapse. It was concluded that although NMDA-mediated potentiation may facilitate kindling, synaptic potentiation does not appear to be a critical requirement for kindling to develop. These findings support the notion that development of the burst response and not synaptic enhancement may be the critical physiological alteration that underlies the kindling phenomenon.
NSI Technology Services Corporation, Research Triangle Park, NC 27711.
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Mack
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate; D051381:Rats; D012016:Reference Values; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate