Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats

Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats

Author Amorim, Beatriz Oliveira Google Scholar
Hamani, Clement Google Scholar
Ferreira, Elenn Google Scholar
Miranda, Maisa Ferreira Google Scholar
Fernandes, Maria Jose S. Google Scholar
Rodrigues, Antonio M. Google Scholar
de Almeida, Antonio-Carlos G. Google Scholar
Covolan, Luciene Google Scholar
Abstract Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A(1) receptors. A(1) 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 A(1) receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A(1) receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A(1) 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 (25 mu g/kg) or DPCPX (50 mu g/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 A(1) agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A(1) receptor antagonists increased both. (C) 2016 Elsevier Inc. All rights reserved.
Keywords Adenosine
Animal models
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor FAPESP
Grant number FAPESP: 2011/50680-2
FAPESP: 2012/50950-2
FAPESP: 2012/10764-5
FAPEMIG: PPM 00283/14
CNPq: 310649/2011-0
Finep ((CT-SAUDE E FNS): 1264/13
Date 2016
Published in Epilepsy & Behavior. San Diego, v. 61, p. 168-173, 2016.
ISSN 1525-5050 (Sherpa/Romeo, impact factor)
Publisher Academic Press Inc Elsevier Science
Extent 168-173
Origin http://dx.doi.org/10.1016/j.yebeh.2016.05.036
Access rights Closed access
Type Article
Web of Science ID WOS:000381248000030
URI https://repositorio.unifesp.br/handle/11600/57467

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