title: The effects of group III mGluR ligands on pentylenetetrazol-induced kindling of seizures and hippocampal amino acids concentration.
abstract: Considering the contribution of hippocampal formation and glutamate-mediated signalling to epileptogenesis, we investigated the effects of group III metabotropic glutamate receptor (mGluR)-selective ligands on the kindling of seizures. We also examined the concentration of the amino acid glutamate, GABA, alanine and taurine in the hippocampus of rats using a microdialysis technique. Pentylenetetrazol (PTZ), a non-competitive antagonist of the GABA(A) receptor, was administered intraperitoneally at 35 mg/kg body weight to induce seizures. It was determined that the kindling of PTZ-induced seizures could be attenuated by post intracerebroventricular administration of 100 nmol of the group III mGluR antagonist CPPG [(RS)-a-cyclopropyl-4-phosphonophenylglycine]. There were significant differences in tested parameters during the final stages of the kindling procedure. The group III mGluR agonist L-AP4 [L-(+)-2-amino-4-phosphonobutyric acid at 100 nmol, i.c.v.] did not significantly affect the kindling of seizures in comparison to control rats, although there was acceleration of the process as compared to CPPG treated animals. We demonstrated that the baseline concentrations of glutamate, GABA, alanine, taurine, and the glutamine/GABA ratio were elevated in the hippocampus of fully kindled rats. Intracerebroventricular administration of a single dose of CPPG increased the concentrations of glutamate in the hippocampus of control, non-kindled rats. Intracerebroventricular administration of L-AP4 did not affect the hippocampal amino acid concentration in either animal group. Overall, these data suggest that there is a shift in the balance between neurotransmitters towards increased production of excitatory amino acids, and this may be mediated by group III mGluRs during seizure kindling.
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland. piomac@yahoo.com
authors.forename: Piotr
authors.initials: P
authors.lastname: Maciejak
authors.forename: Janusz
authors.initials: J
authors.lastname: Szyndler
authors.forename: Danuta
authors.initials: D
authors.lastname: Turzyńska
authors.forename: Alicja
authors.initials: A
authors.lastname: Sobolewska
authors.forename: Ewa
authors.initials: E
authors.lastname: Taracha
authors.forename: Anna
authors.initials: A
authors.lastname: Skórzewska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lehner
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bidziński
authors.forename: Adam
authors.initials: A
authors.lastname: Hamed
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wisłowska-Stanek
authors.forename: Adam
authors.initials: A
authors.lastname: Płaźnik
mesh_terms: D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003292:Convulsants; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000613:Aminobutyrates; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104331:cyclopropyl-4-phosphonophenylglycine; C102718:metabotropic glutamate receptor 3; D013654:Taurine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C012729:2-amino-4-phosphonobutyric acid; D000409:Alanine; D005998:Glycine; D010433:Pentylenetetrazole