Differential sensitivity of genetically Fast vs. Slow kindling rats strains to GABAergic convulsive agents

Following selective breeding for seizure-proneness vs. seizure-resistance to amygdala kindling, two strains of rats were developed with non-overlapping kindling rates, i.e. the number of stimulations required to develop fully generalized convulsive seizures (Epilepsy Res. 35 (1999) 183). In the temporal cortices of these two strains, the local seizure thresholds to electrical stimulation have been reported to be approximately two times lower in the seizure-prone (Fast kindling) compared to the seizure-resistant (Slow kindling) strain (McIntyre et al., 1999). In the present experiment, the pharmacological sensitivities of the two strains to three GABAergic antagonists, pentylenetetrazol, bicuculline and picrotoxin, were determined, and compared to the glycine antagonist, strychnine. Paralleling kindling epileptogenesis, naïve rats of the Fast kindling strain developed convulsive seizures to doses of the GABAergic antagonists that were significantly (approximately 30%) lower than the naïve Slow kindling strain. In contrast, there were no strain differences in their response to strychnine. These data indicate substantial GABAergic sensitivity differences between the two strains with an emphasis on forebrain mechanisms, which is consistent with other physiological and molecular data related to their differential profiles of epileptogenesis.