PENTYLENETETRAZOL-INDUCED KINDLING - EARLY INVOLVEMENT OF EXCITATORY AND INHIBITORY SYSTEMS

Alterations in the brain of rats receiving a single non-convulsive adm inistration pentylenetetrazol (PTZ), 30 mg/kg, i.p. (single PTZ group) were investigated and compared with those detected in fully PTZ kindl ed rats (chronic PTZ group). In vitro receptor autoradiography experim ents showed that both single and chronic PTZ groups presented reduced mu opioid and benzodiazepine (BDZ) receptor binding in specific brain areas. Using an antibody generated against the delta opioid receptor ( DOR-1), it was found that DOR-1 like immunoreactivity was reduced in c ortex and amygdala of mice following single and chronic PTZ administra tion. Microdialysis experiments revealed that the administration of PT Z 30 mg/kg, i.p. in freely moving rats without previous experience wit h the drug, induces a rise in glutamate release, detected in the first and second 10 min dialysates collected from amygdala (138% and 50%, r espectively) and frontal cortex (70% and 45%, respectively) as well as aspartate in frontal cortex in the first and second post-PTZ dialysat es (143% and 80%, respectively). Subsequently, values returned to basa l conditions. It may be speculated that decreased BDZ receptor binding results from enhanced release of GABA. On the other hand, the decreas e of mu receptor binding and DOR-1 immunoreactivity observed after PTZ administration may be the result of enhanced levels of opioid peptide s probably released over the kindling procedure. In conclusion, the pr esent study indicates that PTZ-kindling is associated with an imbalanc e between excitatory and inhibitory systems which is apparent early in the epileptogenic process.