Epilepsy Research 49 (2002) 73 – 80 Inhibitory role of the zona incerta in the pilocarpine model of epilepsy Clement Hamani a, *, Sumire Sakabe a , Zuner A. Bortolotto b , Esper A. Cavalheiro b , Luiz E.A.M. Mello a a Depto de Fisiologia, EPM-UNIFESP, Sao Paulo -SP 04023 -900, Brazil b Depto de Neurologia Experimental, EPM-UNIFESP, Sao Paulo -SP 04023 -900, Brazil Received 26 October 2001; received in revised form 31 January 2002; accepted 5 February 2002 Abstract 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 mus- cimol 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. © 2002 Published by Elsevier Science B.V. Keywords: Epilepsy; GABA; Subthalamic nucleus; Pilocarpine; Zona incerta; Vagus nerve stimulation www.elsevier.com/locate/epilepsyres 1. Introduction Seizure activity can be readily triggered after either intracerebral or systemic administration of cholinergic agonists, particularly pilocarpine (Mello et al., 1993; Turski et al., 1983, 1985). Administration of such agents is able to trigger from pure electroencephalographic phenomena to motor convulsant activity, eventually evolving to status epilepticus (Mello et al., 1993; Turski et al., 1983, 1985). The structural neural substrate involved in the epileptiform activity induced by pilocarpine has been the subject of extensive research (Handforth and Treiman, 1995). Limbic structures in particu- lar, have received substantial attention regarding * Corresponding author. Present address: r. Dr. Luiz Migliano, 761 apt 142c, 05711-001 Sao Paulo-SP, Brazil. Tel./ fax: +55-11-5579-2033. E-mail addresses: chamani@uol.com.br (C. Hamani), lemello@ecb.epm.br (L.E.A.M. Mello). 0920-1211/02/$ - see front matter © 2002 Published by Elsevier Science B.V. PII:S0920-1211(02)00017-7