capsazocaine and Disease-Models--Animal

Intracellular calcium plays an important role in neuronal hyperexcitability that leads to seizures. One calcium influx route of interest is the transient receptor potential vanilloid type 1 (TRPV1) channel. Here, we evaluated the effects of capsazepine (CPZ), a potent blocker of TRPV1 channels on acoustically evoked seizures (audiogenic seizures, AGS) in the genetically epilepsy-prone rat (GEPR-3), a model of inherited epilepsy.. Male and female GEPR-3s were used. For the acute CPZ treatment study, GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of CPZ (0, 1, 3, and 10 mg/kg; ip). For semichronic CPZ treatment study, GEPR-3s were tested for AGS susceptibility before and after 5-day CPZ treatment at the dose of 1 mg/kg (ip). The prevalence, latency, and severity of AGS were recorded and analyzed.. We found that acute CPZ pretreatment reduced the seizure severity in male GEPR-3s; the effect was dose-dependent. In female GEPR-3s, however, CPZ treatment completely suppressed the seizure susceptibility. Furthermore, semichronic CPZ treatment suppressed seizure susceptibility in female GEPR-3s, but only reduced the seizure severity in male GEPR-3s.. These findings suggest that the TRPV1 channel is a promising molecular target for seizure suppression, with female GEPR-3s exhibiting higher sensitivity than male GEPR-3s.

Topics: Acoustic Stimulation; Analysis of Variance; Animals; Anticonvulsants; Benzoates; Body Temperature; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy; Female; Kindling, Neurologic; Male; Oxazoles; Rats; Rats, Mutant Strains; Sex Factors; Time Factors; TRPV Cation Channels