Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model

Effective prophylaxis for post-traumatic epilepsy currently does not exist, and clinical trials using anticonvulsant drugs have yielded no long-term antiepileptogenic effects. We report that a single, rapid post-traumatic application of the proconvulsant cannabinoid type-1 (CB1) receptor antagonist SR141716A (Rimonabant-Acomplia (R)) abolishes the long-term increase in seizure susceptibility caused by head injury in rats. These results indicate that, paradoxically, a seizure-enhancing drug may disrupt the epileptogenic process if applied within a short therapeutic time window. (C) 2009 Elsevier B.V. All rights reserved.