Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats

摘要: SummaryObjective Although drugs targeting the cannabinoid system (e.g., CB1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures/epilepsy, they remain unexplored developing models. However, functions emerge early development, providing a rationale for this neonates. We examined therapeutic potential three seizure rats. Methods Postnatal day (P) 10, Sprague–Dawley rat pups were challenged with chemoconvulsant methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) or pentylenetetrazole (PTZ), after treatment either CB1/2 mixed agonist (WIN 55,212-2), (arachidonyl-2′-chloroethylamide [ACEA]), CB2 (HU-308), antagonist (AM-251), (AM-630), fatty acid amide hydrolase inhibitor (URB-597), G protein–coupled 55 (O-1602). P20 DMCM WIN, ACEA, URB. Finally, pretreatment P10 rats against acute hypoxia-induced seizures. Results The and CB1-specific agonist, but no other drugs, displayed effects clonic seizures model. By contrast, both antagonism increased severity. Similarly, we found that antiseizure (automatisms, tonic–clonic seizures) evoked by PTZ. Anticonvulsant seen animals not animals. Significance Early life represent significant cause morbidity, 30–40% infants children epilepsy failing to achieve remission current pharmacotherapy. Identification new therapies neonatal/infantile syndromes is thus high priority. These data indicate action CB specific activation during development provide justification further examination agonists as novel antiepileptic children.