Inhibitory role of the zona incerta in the pilocarpine model of epilepsy.

Recent experiments have suggested that the zona incerta might be regarded as a highly sensitive structure for seizure induction. This sensitivity has been linked to this structure's abundant expression of cholinergic receptors. Here we have decided to investigate the participation of the GABAergic system of the zona incerta, one of its major neurotransmitters with widespread projections to the neocortex, in the pilocarpine (Pilo) model of epilepsy. Stereotaxic administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or saline (controls) bilaterally into the zona incerta of adult male Wistar rats was performed 30 min prior to the systemic injection of pilocarpine. Animals were electroencephalographically and behaviorally monitored for seizure activity. Administration of muscimol had a pro-convulsant effect characterised by a higher percentage of animals developing SE with a shorter latency. Conversely, administration of bicuculline had a dose dependent anticonvulsant effect, with no animals displaying SE. Our results contribute to the further characterisation of the regulatory role of the zona incerta in seizure-related phenomena, suggesting that its modulation might be a relevant target for anticonvulsant strategies.