Developing Genetically Epilepsy‐Prone Rats Have an Abnormal Seizure Response to Flurothyl

Abstract

Development of clonic-tonic flurothyl-induced seizures was examined in both normal and genetically epilepsy-prone rats (GEPRs). At each age, from 10 to 30 days, clonus occurred at significantly shorter latencies in GEPRs than in normal rats. The latency to onset of clonic seizures did not change with age, however, in either GEPRs or normal rats. A different pattern of response was observed in the progression to tonic seizures. As normal animals matured, the latency to tonic seizures became longer and, by day 30, the duration of flurothyl exposure necessary to induce tonus was almost 70% greater in normal rats than in the GEPRs. In contrast, in GEPRs, tonic extension occurred immediately following the onset of clonus throughout development. A subset of GEPRs failed to have audiogenic seizures in a 40-day posttest. These animals had a flurothyl response identical to their audiogenic-susceptible litter mates. These data suggest that (a) a protective mechanism which develops against tonic seizures in normal rats fails to mature in the GEPR, and (b) seizure inducing gene-linked neural abnormalities occur in the GEPR independent of pathologies underlying audiogenic seizures.

The role of norepinephrine in epilepsy: from the bench to the bedside

“…Seizure severity is higher in GEPR-9 compared with GEPR-3, as confirmed by the observation that after an acoustic stimulus GEPR-3 rats show only mild clonic seizures, while GEPR-9 exhibit massive tonic and tonicclonic seizures [122]. Both strains possess a reduced threshold to various epileptic stimuli, such as electroshock and PTZ [123], flurothyl ether [124], limbic kindling [125].…”

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity

“…1) as has been previously described (Ferland and Applegate, 1999, Franck, et al, 1989, Hashimoto, et al, 2006, Oommen, et al, 2007, Papandrea, et al, 2009, Samoriski and Applegate, 1997, Stafstrom, et al, 1992); however, concentrations of flurothyl necessary for generalized seizure expression are also reported (Table 1). All C57BL/6J (B6) mice tested in the repeated-flurothyl model had a high initial latency to generalized seizure expression compared to DBA/2J (D2) mice, which significantly decreased over the course of eight repeated flurothyl exposures, plateauing on seizure trial 5 (Fig.…”

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

“…Several studies of sound-induced [109][110][111] and flurothyl-induced [112] seizures have provided ontogenetic data on GEPRs, showing that seizure incidence and severity develop as a function of maturation in GEPR pups. In a short time period, sound-induced brainstem seizures seem to give rise to secondarily ignited forebrain seizures.…”

“…The seizures in GEPRs are induced by aminophylline and other xanthines alone or in coadministration with quinolones [96,144,145], electroshock [146], flurothyl [112], hyperbaric conditions [147], pentylenetetrazol [146], and barbiturate withdrawal [148] and some typical/atypical antipsychotics [149].…”