title: Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats.
abstract: Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A1 receptors. A1 receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A1 receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A1 receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A1 antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25μg/kg) or DPCPX (50μg/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A1 agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A1 receptor antagonists increased both.
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Beatriz Oliveira
authors.initials: BO
authors.lastname: Amorim
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: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Elenn
authors.initials: E
authors.lastname: Ferreira
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei, São João del-Rei, Brazil.
authors.forename: Maísa Ferreira
authors.initials: MF
authors.lastname: Miranda
authors.affiliation: Disciplina de Neurologia Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Maria José S
authors.initials: MJS
authors.lastname: Fernandes
authors.affiliation: Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei, São João del-Rei, Brazil.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Rodrigues
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: AG
authors.lastname: de Almeida
authors.affiliation: Disciplina de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address: lucovolan@gmail.com.
authors.forename: Luciene
authors.initials: L
authors.lastname: Covolan
mesh_terms: D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D003292:Convulsants; D018721:Muscarinic Agonists; D014970:Xanthines; D010862:Pilocarpine; D010660:Phenylisopropyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine
keywords: Adenosine; Animal models; Electrophysiology; Epilepsy; Hippocampus; Seizures