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J Physiol Pharmacol ; 71(4)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33316769

RESUMO

The lithium-pilocarpine model in rats is commonly used to study the characteristic events of acute status epilepticus (SE), epileptogenesis and temporal lobe epilepsy (TLE). Here we investigated the impact of lacosamide alone and in combination with other drugs (pregabalin, piracetam and scopolamine) on spontaneous recurrent seizures (SRSs) and behavioral parameters during the time frame of 6 weeks after SE. In addition, the level of oxidative stress in the hippocampus was accessed by real-time microdialysis study (8-isoprostanes) and antioxidants enzymes in the homogenate. Results revealed severe behavioral deficits with the control epileptic group and animals displayed hyperexcitability, aggression apprehension and memory insufficiency. Pharmacological manipulation for 6 weeks with lacosamide (L) - 80 mg/kg; in polypharmacy with pregabalin (L/P) - 50/50 mg/kg and piracetam (L/Pi) - 50/140 mg/kg significantly (P < 0.05) ameliorated the anxiety-related behavior (open filed, elevated plus maze, light/dark tests), depression (forced swim test) and improved spatial/reference memory (Morris water maze). There were low incidences of seizures in L, L/P and L/Pi groups revealing disease-modifying effects of employed drugs. Furthermore, the chronic use of scopolamine (L/P/S; 50/50/2 mg/kg) as polypharmacy with the concept of antagonizing the cholinergic inputs in the epileptogenic phase aberrated the behavioral situation further worse. Treatments with L/P and L/Pi significantly attenuated (P < 0.05) the oxidative stress by reducing 8-isoprostanes and malondialdehyde (MDA) levels. Furthermore, superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in the L/P group were significantly (P < 0.05) improved. Overall, our findings support the use of a combination of drugs (L/P and L/Pi) in lithium-pilocarpine model which remarkably ameliorated SRSs, reduced anxiety-related behaviors, retention of spatial/reference memory and lowered oxidative stress in a time-course evaluation 6 weeks post- SE insult.


Assuntos
Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lacosamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estado Epiléptico/prevenção & controle , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Teste de Campo Aberto/efeitos dos fármacos , Pilocarpina , Ratos Sprague-Dawley , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/psicologia , Natação , Fatores de Tempo
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