Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy-prone rat.
CNS Neurosci Ther
; 24(1): 18-28, 2018 Jan.
Article
in En
| MEDLINE
| ID: mdl-29105300
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epilepsy
/
TRPV Cation Channels
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
CNS Neurosci Ther
Journal subject:
NEUROLOGIA
/
TERAPEUTICA
Year:
2018
Document type:
Article
Affiliation country:
United States