Abstracts

Rationale: Animal models are valuable tools to study how genetic predisposition influences the development of acquired epilepsies. Previously, Racine and colleagues (1999) have developed rat strains selectively bred for differences in the susceptibility to evoked seizures: defined as seizure-prone (FAST) or seizure-resistant (SLOW) in the amygdala kindling model, a well-validated model of acquired epilepsy. This study aimed to validate this animal model and confirm the phenotypes of our current colony generations of FAST, SLOW and to evaluate the seizure susceptibility of their F2 progeny (generated by crossing FAST and SLOW rats) after experimental amygdala kindling.

Methods: 11-week-old male rats—FAST (n = 10), SLOW (n = 14) and their F2 generation (n = 68)—underwent an electrode implantation surgery. A stimulating bipolar electrode was inserted in the left amygdala (Coordinates from Bregma: AP −3 mm, ML 5.2 mm and DV 8.9 mm), and epidural screw electrodes were implanted into the ipsilateral (AP −1.7 mm, ML 4.0 mm) and contralateral (AP −3 mm, ML -5.2 mm) side of the brain. Ground and reference electrodes were inserted in the skull overlying the cerebellum. One week post-surgery, the after-discharge (AD) threshold of the rats was determined and defined as the minimum current (1.7 millisecond interval, 1 sec pulse duration, 60 Hz sine wave stimulus of increasing intensity 100-400 μA) required to produce an electrographic seizure for > 5 sec. Rats then either received a maximum of 30 kindling stimulations (2 stimulations/day, 5 days a week) or until 5 class V seizures were observed (fully kindled) with the same amplitude as their AD threshold. Classification of seizures was based on the Racine scale.

Results: FAST rats required significantly fewer stimulations to reach a fully kindled state compared to SLOW rats (p < 0.001), with all animals fully kindled within 30 stimulations. The F2 generation required significantly fewer stimulations to reach fully kindled compared to the SLOW rats (p < 0.01) but did not show any significant differences to the FAST rats. Strain differences were also evident in the number of stimulations to reach seizure classes III to V, with SLOW rats requiring a significantly higher number of stimulations to reach these seizure classes compared to the FAST rats, and the F2 rats falling in between FAST and SLOWs. Lastly, total duration of seizures was also significantly shorter for the SLOW rats compared to the FAST and F2 rats for the first 12-18 stimulations.