Hippocampal and cerebellar extracellular amino acids during pilocarpine-induced seizures in freely moving rats.
Limbic seizures were provoked in freely moving rats by intrahippocampal administration of the muscarinic receptor agonist pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microliters/min). Changes in extracellular hippocampal and cerebellar glutamate, aspartate and gamma-aminobutyric acid (GABA) levels were monitored during and after pilocarpine administration. Effects of systemic or local administration of anticonvulsants on the seizures and concomitant changes in amino-acid concentrations, were investigated. Pilocarpine-induced seizures were completely abolished after intraperitoneal premedication for 7 days with phenobarbital (15 mg/kg per day) and after intrahippocampal administration of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2 microliters/min). Rats premedicated with carbamazepine (5 mg/kg per day) still developed seizures. The changes in extracellular hippocampal amino-acid levels suggest that glutamate, aspartate and GABA are not involved in seizure onset, but may play a role in seizure maintenance and/or spread in the pilocarpine animal model of epilepsy. The increases in extracellular amino acids in ipsi- and contralateral cerebellum following limbic seizures provoked in the hippocampus, probably play a role in the 'reversed' diaschisis phenomenon.
Smolders
I
I
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universteit Brussel, Belgium.
Van Belle
K
K
Ebinger
G
G
Michotte
Y
Y
D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis; D002220:Carbamazepine / Q000494:pharmacology; D002531:Cerebellum / Q000737:chemistry*; D018698:Glutamic Acid / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry*; D008297:Male; D017551:Microdialysis; D010634:Phenobarbital / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D000596:Amino Acids; D010862:Pilocarpine; D001224:Aspartic Acid; D002220:Carbamazepine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D010634:Phenobarbital