Sensitivity and density of glutamate receptor subtypes in the hippocampal formation are altered in pentylenetetrazole-kindled rats.
Kindling induced by 13 intraperitoneal injections of 40 mg/kg pentylenetetrazole (PTZ) over a period of 4 weeks resulted in a significant long-lasting increase in both the convulsive susceptibility of animals to the convulsant and the density of the specific [3H]-L-glutamate binding sites in the hippocampus. The quisqualate- and kainate-sensitive [3H]-L-glutamate binding sites were increased 24 h after the final PTZ injection, whereas the N-methyl-D-aspartate (NMDA)-sensitive sites had only a tendency to be enhanced. Furthermore, we investigated [3H]-L-glutamate binding on metabotropic receptors and found a significant increase in the hippocampus following PTZ kindling. In addition, in hippocampal tissue of kindled rats (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)-stimulated inositol phosphate formation is increased. It can be concluded that the increase in metabotropic glutamate receptor (mGluR) density may be the expression of a specific enhancement in susceptibility of the glutamatergic systems to this excitatory amino acid developing in the course of PTZ-induced kindling.
Schroeder
H
H
Institute of Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. helmut.schroeder@medizin.uni-magdeburg.de
Becker
A
A
Hoellt
V
V
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry*; D007295:Inositol Phosphates / Q000378:metabolism; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010433:Pentylenetetrazole; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism; D017470:Receptors, Glutamate / Q000032:analysis* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000032:analysis / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism; D014316:Tritium
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003292:Convulsants; D003515:Cycloleucine; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007295:Inositol Phosphates; D018696:Neuroprotective Agents; D010433:Pentylenetetrazole; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C036361:1-amino-1,3-dicarboxycyclopentane; C069052:CGP 39653