Evidence for G protein modulation of experimental-generalized absence seizures in rat

Pertussis toxin is known to inhibit G proteins via ADP-ribosylation, and a response to pertussis toxin is presumptive evidence of G protein modulation of the activity being studied. Therefore, in order to test the hypothesis that G protein-mediated mechanisms are involved in the pathogenesis of generalized absence seizures, the effect of pertussis toxin in two pharmacological models of generalized absence seizures in rat was investigated. The experimental absence seizure models used were the gamma-hydroxybutyrate (GHB) model and low dose pentylenetetrazole (PTZ) model in rat. Pretreatment with pertussis toxin administered intracerebroventricularly (i.c.v.) resulted in a significant decrease in duration of seizure in both models. These data suggest that G-protein-mediated mechanisms may be involved in the pathogenesis of the bilaterally synchronous spike wave discharges (SWD) that characterize experimental absence seizures.