A NEUROPHARMACOLOGICAL ANALYSIS OF PTZ-INDUCED KINDLING IN MICE

1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic ch anges associated with epileptic features. 2. The aim of this studs was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and a nalyze glutamatergic changes associated with this phenomena. 3. A sign ificant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, signific antly increased (169.8%) the specific binding of [H-3]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice w as prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ- induced kindling and that, as in rats, the kindling increases the spec ific [H-3]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes bel ieved to underlie epileptic phenomena. (C) 1998 Elsevier Science Inc.