AMPA receptor activation reduces epileptiform activity in the rat neocortex.
We have previously reported that topical application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects of a subsequent application of N-methyl-d-aspartic acid (NMDA). Activation of NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore, we examined if topically applied AMPA could affect changes in the somatosensory evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by bicuculline. AMPA (50 microM) prevented the epileptiform activity to a level that was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100 mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. In the hippocampal slice, bicuculline-induced changes in the population spike potentials recorded from the CA1 cells were not affected by AMPA. We conclude that in the complex neuronal network of the rat neocortex, epileptiform activity can be suppressed in a variety of strategies that target the AMPA receptors: (1) blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA receptors (possibly on the pyramidal neurons) or (3) reducing an apparent desensitization of AMPA receptors (possibly on the inhibitory GABA-ergic interneurons).
Addae
Jonas I
JI
Department of Preclinical Sciences, Faculty of Medical Sciences, University of the West Indies, St. Augustine Campus, Trinidad and Tobago. jaddae@fms.uwi.tt
Ali
Nakisha
N
Youssef
Farid F
FF
Stone
Trevor W
TW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001581:Benzothiadiazines / Q000494:pharmacology; D001640:Bicuculline; D002719:Chlormethiazole / Q000494:pharmacology / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D001581:Benzothiadiazines; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D002719:Chlormethiazole; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide; D003975:Diazepam; D001640:Bicuculline