title: Role of adenosine in the antiepileptic effects of deep brain stimulation.
abstract: Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
authors.forename: Maisa F
authors.initials: MF
authors.lastname: Miranda
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo São Paulo, Brazil ; Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health Toronto, Canada ; Division of Neurosurgery, Toronto Western Hospital, University of Toronto Toronto, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
authors.forename: Antônio-Carlos G
authors.initials: AC
authors.lastname: de Almeida
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Beatriz O
authors.initials: BO
authors.lastname: Amorim
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Macedo
authors.affiliation: Disciplina de Neurologia Experimental, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Maria José S
authors.initials: MJ
authors.lastname: Fernandes
authors.affiliation: Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health Toronto, Canada.
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
authors.forename: Mayra C
authors.initials: MC
authors.lastname: Aarão
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Madureira
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
authors.forename: Antônio M
authors.initials: AM
authors.lastname: Rodrigues
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Mello
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo São Paulo, Brazil.
authors.forename: Luciene
authors.initials: L
authors.lastname: Covolan
keywords: adenosine; anterior nucleus; deep brain stimulation; epilepsy; seizures; thalamus