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 changes associated with epileptic features. 2. The aim of this studs was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant 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, significantly increased (169.8%) the specific binding of [H-3]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was 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 specific [H-3]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena. (C) 1998 Elsevier Science Inc.