Effect of ionotropic glutamate receptors antagonists on the modifications in extracellular glutamate and aspartate levels during picrotoxin seizures: a microdialysis study in freely moving rats.
Our previous studies have shown a local decrease in glutamate and aspartate levels during seizures, induced by picrotoxin microdialysis in the hippocampus of chronic freely moving rats. In this paper, we study the effect of continuous hippocampal microperfusion of the NMDA, AMPA and kainate glutamate receptor inhibitors 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801); 6,7-dinitroquinoxaline-2,3-dione (DNQX), and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466). We also examine the action of L(-)-threo-3-hydroxyaspartic acid (THA), a glutamate and aspartate reuptake blocker, on the modification of extracellular glutamate and aspartate levels induced by picrotoxin, using the microdialysis method in freely moving rats. We found that changes in extracellular hippocampal concentrations in both amino acids are prevented by NMDA, AMPA and kainate receptor inhibitors. Seizures elicited under DNQX also induce a transient increase in aspartate extracellular levels coincident with seizure time. L(-)-threo-3-hydroxyaspartic acid increased the basal extracellular concentrations of both amino acids, but did not prevent the seizure-related decrease. Our results suggest that glutamate, the major neurotransmitter at the synaptic level, may also play an important role in non-synaptic transmission during seizures.
Sierra-Paredes
G
G
Neuroscience Division, Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago, San Francisco 1, 15705, Santiago de Compostela, Spain. bngersp@usc.es
Galán-Valiente
J
J
Vazquez-Illanes
M D
MD
Aguilar-Veiga
E
E
Sierra-Marcuño
G
G
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001569:Benzodiazepines; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010852:Picrotoxin; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001224:Aspartic Acid; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin; D011810:Quinoxalines; D017470:Receptors, Glutamate; C061950:GYKI 52466; C011274:3-hydroxyaspartic acid; C056723:FG 9041