Aims
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.
Methods
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.
Results
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.
Conclusions
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.