Role of adenosine in the antiepileptic effects of deep brain stimulation

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 epileptiforrn 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)AFIP (Associacao Fundo de Incentivo a Pesquisa)Univ Fed Sao Joao del Rei, Lab Neurociencia Expt & Computac, Sao Joao Del Rei, BrazilUniversidade Federal de São Paulo, Disciplina Neurofisiol, São Paulo, BrazilCtr Addict & Mental Hlth, Behav Neurobiol Lab, Toronto, ON, CanadaUniv Toronto, Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, CanadaUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurofisiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Expt, São Paulo, BrazilFAPESP: 2011150680-2FAPESP: 50950-2Web of Scienc