HIPPOCAMPAL AND CEREBELLAR EXTRACELLULAR AMINO-ACIDS DURING PILOCARPINE-INDUCED SEIZURES IN FREELY MOVING RATS

Limbic seizures were provoked in freely moving rats by intrahippocampa l administration of the muscarinic receptor agonist pilocarpine via a microdialysis probe (10 mM for 40 min at 2 mu l/min). Changes in extra cellular hippocampal and cerebellar glutamate, aspartate and gamma-ami nobutyric acid (GABA) levels were monitored during and after pilocarpi ne administration. Effects of systemic or local administration of anti convulsants on the seizures and concomitant changes in amino-acid conc entrations, were investigated. Pilocarpine-induced seizures were compl etely abolished after intraperitoneal premedication for 7 days with ph enobarbital (15 mg/kg per day) and after intrahippocampal administrati on of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2 mu l/mi n). Rats premedicated with carbamazepine (5 mg/kg per day) still devel oped seizures. The changes in extracellular hippocampal amino-acid lev els suggest that glutamate, aspartate and GABA are not involved in sei zure onset, but may play a role in seizure maintenance and/or spread i n the pilocarpine animal model of epilepsy. The increases in extracell ular amino acids in ipsi- and contralateral cerebellum following limbi c seizures provoked in the hippocampus, probably play a role in the 'r eversed' diaschisis phenomenon.