Marked strain and substrain differences in induction of status epilepticus and subsequent development of neurodegeneration, epilepsy, and behavioral alterations in rats: Strain and substrain differences in an epilepsy model in rats

Abstract

Outbred rat strains such as Sprague-Dawley (SD) or Wistar are widely used in epilepsy models, including popular models of temporal lobe epilepsy in which spontaneous recurrent seizures (SRS), hippocampal damage, and behavioral alterations develop after status epilepticus (SE). Such rats are randomly outbred, hence allelic variations can occur across separate colonies, so that outbred rats from different sources may have little in common with each other besides their names and similarities in pelage. Although such intrastrain differences may be an important reason for discrepancies between studies from different laboratories, the extent to which such differences affect development of seizures, neurodegeneration, and psychopathology in post-SE models of epilepsy has received little attention as yet. In the present study, we induced SE by sustained electrical stimulation of the basolateral amygdala in SD and Wistar rats from different breeders (Harlan, Charles River, Janvier, Taconic) as well as different breeding locations of the same breeder (Harlan-Winkelmann in Germany vs. Harlan in the Netherlands). Several marked inter- and intrastrain differences in induction of SE and its long-term consequences were found. Wistar rats from different vendors were all strikingly less sensitive to SE induction than SD rats from Harlan-Winkelmann or Harlan. Within the SD strain, SD rats from Charles River exhibited markedly lower sensitivity to SE induction than all other groups of SD rats. The majority of SD rats from different vendors developed SRS after SE except SD rats from Charles River. The latter rats also markedly differed in basal behavior, SE-induced behavioral alterations and neurodegeneration from other SD substrains. These marked inter- and intrastrain differences provide an interesting tool to study the impact of genetic and environmental factors on seizure susceptibility, epileptogenesis, and the relationship between behavior and epilepsy and vice versa.