The effect of the cannabinoid-receptor antagonist, SR141716, on the early stage of kainate-induced epileptogenesis in the adult rat.

Pretreatment with the endocannabinoid-receptor antagonist, SR141716, has been reported to suppress the long-lasting hyperexcitability and increased seizure susceptibility present after 30 min of hyperthermia-induced convulsions in immature rats, an animal model of complex febrile seizures in children, which may be a cause of temporal lobe epilepsy. The present experiments tested the hypothesis that SR141716 suppresses epileptogenesis in the adult kainate model, an animal model of temporal lobe epilepsy. Adult male rats (n = 35), implanted for electroencephalography (EEG) recordings, were treated with kainate. Immediately after the first acute electrographic seizure during kainate-induced status epilepticus, either vehicle or SR141716 (10 mg/kg) was injected intraperitoneally. Chronic video-EEG data were collected for the first 2-week period after kainate-induced status epilepticus. More than one-half of both the vehicle- and drug-treated animals showed spontaneous recurrent seizures. Similarly, mean seizure frequency did not differ significantly for the drug- and vehicle-treated animals during the first 2 weeks (n = 9 and 8, respectively). Therefore, no significant differences were found between SR141716-treated and control animals during the first 2 weeks of epileptogenesis. These results suggest that the endocannabinoid-receptor antagonist, SR141716, had no detectable effect on the early stages of epileptogenesis in the adult kainate model. We discuss several potential explanations for the differences in the effects of SR141716 in the adult-rat, kainate versus immature-rat, hyperthermia models.