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

Abstract

SummaryPre-treatment 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 electroencephalogram (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 intraperitoneal. Chronic video-EEG data were collected for the first 2-week period after kainate-induced status epilepticus. Over half of both the vehicle-and drugtreated animals showed spontaneous recurrent seizures. Similarly, mean seizure frequency was not significantly different for the drug-and vehicle-treated animals during the first 2 weeks (n=9 and 8, respectively). Thus, 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. Several potential explanations for the differences in the effects of SR141716 in the adult-rat, kainate versus immature-rat, hyperthermia models are discussed.

Analysis in conditional cannabinoid 1 receptor-knockout mice reveals neuronal subpopulation-specific effects on epileptogenesis in the kindling paradigm

“…In apparent contrast, van Rijn et al (2011) reported that the CB1R antagonist rimonabant can exert a pro-epileptogenic effect after chronic administration in naïve rats (van Rijn et al, 2011). Another study in the kainate model of temporal lobe epilepsy did not report relevant effects of rimonabant on epileptogenesis (Dudek et al, 2010). Considering these controversial findings, it is obviously necessary to further explore the role of CB1Rs in epileptogenesis in more detail.…”

“…The detailed etiology of epileptogenesis remains unknown, and whether the endocannabinoid system is involved in epileptogenesis and promotes anti-or proconvulsant effects is still controversially discussed (Dudek et al, 2010;Echegoyen et al, 2009). This might be partly related to the dichotomous role of endocannabinoid signaling in different neuronal subpopulations.…”

Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke

“…21 Animal models of neonatal brain injury also support an association between neonatal seizures and epilepsy. [22][23][24] Whether seizures in the setting of an acute perinatal stroke have a deleterious effect on developing brain or are simply a marker for greater underlying brain injury is unknown, but the association with childhood epilepsy is worrisome. An active seizure focus in the setting of acute stroke could increase metabolic demand in ischemic penumbra and worsen brain injury, or the presence of neonatal seizures may contribute to epileptogenesis during a crucial developmental window.…”

Prävention von Epilepsien

“…Andererseits konn te z. B. für den Endocannabinoidrezep torantagonisten Rimonabant dargestellt werden, dass lediglich eine sehr frühe Applikation 2 min nach einem experi mentell induzierten SchädelHirnTrau ma mit einem antiepileptogenen Effekt verbunden war, während die Applikation nach 20 min keinen entsprechenden Ef fekt ausübte [6].…”