NMDA receptor antagonists CPP and MK-801 partially suppress the epileptiform discharges induced by the convulsant drug bicuculline in the rat neocortex

Intracellular recordings were obtained from neurons located in the superficial layers of rat neocortical slices maintained in vitro. In the presence of 50 microM of bicuculline methiodide, epileptiform discharges were evoked by extracellular local stimuli. Bath applications of the NMDA receptor antagonists CPP or MK-801 (3-5 microM) produced the following effects: (i) prolongation of the burst latency; (ii) attenuation of the burst duration, mainly its late phase; (iii) increase in the threshold of burst activation. These effects were not accompanied by any change in membrane potential, input resistance and repetitive firing evoked by intracellular pulses of depolarizing current. Our results indicate the involvement of conductances mediated through NMDA receptors in the genesis of epileptiform activities recorded in the neocortex upon blockade of GABA receptors.

[1]  L. Nowak,et al.  Magnesium gates glutamate-activated channels in mouse central neurones , 1984, Nature.

[2]  R. Dingledine.  NMDA Receptors: what do they do? , 1986, Trends in Neurosciences.

[3]  B. Connors,et al.  Electrophysiological properties of neocortical neurons in vitro. , 1982, Journal of neurophysiology.

[4]  M. Avoli.  GABAergic Mechanisms and Epileptic Discharges , 1988 .

[5]  E. Wong,et al.  [3H]MK‐801 Labels a Site on the N‐Methyl‐D‐Aspartate Receptor Channel Complex in Rat Brain Membranes , 1988, Journal of neurochemistry.

[6]  L. Iversen,et al.  The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Watkins,et al.  Anticonvulsant activity of two novel piperazine derivatives with potent kainate antagonist activity , 1985, Neuroscience Letters.

[8]  W. Singer,et al.  Long-term potentiation and NMDA receptors in rat visual cortex , 1987, Nature.

[9]  J. Watkins,et al.  Evidence that antagonism at non-NMDA receptors results in anticonvulsant action. , 1987, European journal of pharmacology.

[10]  R. Dingledine,et al.  Involvement of N-methyl-d-aspartate Receptors in Involvement of N-methyl-d-aspartate Receptors in Epileptiform Bursting in the Rat Hippocampal Slice , 2008 .

[11]  Massimo Avoli,et al.  Inhibitory potentials in neurons of the deep layers of the in vitro neocortical slice , 1986, Brain Research.

[12]  N. Harrison,et al.  Spontaneous paroxysmal activity induced by zero magnesium and bicuculline: suppression by NMDA antagonists and GABA mimetics. , 1986, European Journal of Pharmacology.

[13]  G. Collingridge,et al.  MK-801 blocks NMDA receptor-mediated synaptic transmission and long term potentiation in rat hippocampal slices , 1987, Neuroscience Letters.

[14]  M. Avoli,et al.  Seizure-like discharges induced by lowering [Mg2+]0 in the human epileptogenic neocortex maintained in vitro , 1987, Brain Research.

[15]  A. Thomson,et al.  N-methylaspartate receptors mediate epileptiform activity evoked in some, but not all, conditions in rat neocortical slices , 1986, Neuroscience.

[16]  B. Meldrum,et al.  Anticonvulsant action of excitatory amino acid antagonists. , 1982, Science.

[17]  B. Connors,et al.  Mechanisms of neocortical epileptogenesis in vitro. , 1982, Journal of neurophysiology.

[18]  P. Herrling,et al.  CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]d-AP5 binding sites on brain membranes and anticonvulsant activity , 1986, Brain Research.

[19]  A. Ganong,et al.  Action of 3-((±)-2-car☐ypiperazin-4-yl)-propyl-1-phosphonic aci (CPP): a new and highly potent antagonist of N-methyl-d-aspartate receptors in the hippocampus , 1986, Brain Research.