Abstracts

Previous studies have shown that seizure thresholds vary in different strains of mice. However, there has been little direct comparison across strains in terms of their susceptibility to electrical kindling and chemically-induced seizure thresholds. In the present studies, we compared the seizure susceptibility of four strains of mice: CF-1, a Swiss albino strain commonly used in anticonvulsant studies; CD-1, a non-Swiss albino strain commonly used in pharmacology studies; C57/BL6, an inbred strain and common parental line for transgenic mice; and 129S6/SvEv, a common source for embryonic stem cells and parental line for transgenic mice. We compared the differences among these 4 strains of mice in the amygdala kindling model and in chemically induced acute seizure models. In addition, we determined the anticonvulsant effects of carbamazepine and levetiracetam in kindled mice.
A bipolar electrode was stereotaxically implanted into the right amygdala of CF-1, CD-1, C57/BL6 and 129S6/SvEv mice. Mice were given daily stimulations (500 mA, 60 Hz, 1 sec) until at least 10 stage 5 (Racine scale) seizures occurred. Behavioral seizure scores (Racine scale) and EEG after-discharge (AD) durations were recorded throughout. Post-kindling seizure thresholds and AD durations were also determined. After thresholds stabilized, the anticonvulsant effects of carbamazepine (30 mg/kg, IP) and levetiracetam (50 mg/kg, IP) were determined. In chemically-induced seizure models, kainate (20 mg/kg, IP) or pilocarpine (100 mg/kg, IP) were injected every 20 minutes until the first limbic seizure. The number of doses and minutes to onset of limbic seizures were recorded.
During kindling development, the C57/BL6 mice had higher seizure scores but comparable AD durations compared to the other three strains of mice. Post-kindling, seizure thresholds were not significantly different among the 4 strains, however the 129S6/SvEv strain had longer AD durations. Carbamazepine and levetiracetam increased the seizure thresholds of all strains. In addition, C57/BL6 mice required significantly fewer doses and less time to the onset of limbic seizures, and had more deaths, than the other 3 strains after kainate, whereas 129S6/SvEv mice were relatively more resistant to pilocarpine in that they required higher doses to induce seizures.
C57/BL6 mice were more seizure-prone than CF-1, CD-1 or 129S6/SvEv mice in amygdala kindling and kainate seizure models, whereas 129S6/SvEv mice were less susceptible to pilocarpine-induced seizures. The present results demonstrate that differences among mouse strains exist in seizure susceptibility to amygdala kindling as well as kainate- and pilocarpine-induced seizures. In particular, C57/BL6 mice are relatively more seizure prone, a finding that should be taken into consideration in investigations of transgenic mice with the C57BL/6 strain as one of the parental lines.
[Supported by: Lilly Research Laboratories]