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

Bittencourt, Simone; Dubiela, Francisco P.; Queiroz, Claudio; Covolan, Luciene; Andrade, Danielle; Lozano, Andres; Mello, Luiz E.; Hamani, Clement

doi:10.1016/j.seizure.2010.02.010

« Previous Next »Seizure: European Journal of Epilepsy
Volume 19, Issue 4 , Pages 242-246, May 2010

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

Simone Bittencourt
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
Francisco P. Dubiela
- Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
Claudio Queiroz
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
- Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
Luciene Covolan
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
Danielle Andrade
- Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada
Andres Lozano
- Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
Luiz E. Mello
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
Clement Hamani
- Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil
- Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
- Corresponding author at: Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street WW 4-437, M5T2S8 Toronto, ON, Canada. Tel.: +1 416 6035771; fax: +1 416 6035298.

Received 14 October 2009; received in revised form 12 December 2009; accepted 26 February 2010. published online 29 March 2010.

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 80nmol), bicuculline (15nmol), or saline (controls) 20min prior to pilocarpine administration (350mg/kg i.p.). Electrographic recordings were used to confirm seizure activity. We found that pretreatment with AN muscimol 160nmol 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 80nmol 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.