Microinjection of GABAergic agents into the anterior nucleus of the thalamus modulates pilocarpine-induced seizures and status epilepticus

Abstract

The anterior nucleus of the thalamus (AN) has been suggested as a potential target for seizure modulation in animal models and patients with refractory epilepsy. We investigate whether microinjections of GABAergic agonists into the AN were protective against pilocarpine-induced generalized seizures and status epilepticus (SE). Rats were treated with bilateral AN injections of muscimol (160 or 80 nmol), bicuculline (15 nmol), or saline (controls) 20 min prior to pilocarpine administration (350 mg/kg i.p.). Electrographic recordings were used to confirm seizure activity. We found that pretreatment with AN muscimol 160 nmol increased the latency to seizures and SE by 2.5-3.0-fold. This dose however was associated with side effects, particularly hypotonia. AN bicuculline was proconvulsant, whereas no major effect was observed after muscimol 80 nmol injections. the percentage of animals that developed SE was similar across groups. Overall, microinjection of high doses of muscimol into the AN delayed the occurrence of pilocarpine-induced seizures and SE but was not able to prevent these events. (C) 2010 British Epilepsy Association. Published by Elsevier B.V. All rights reserved.