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Exp Toxicol Pathol ; 67(2): 211-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25547370

RESUMO

Accumulating evidence strongly suggests that gamma amino butyric acid (GABA) receptors play a crucial role in the pathogenesis of Parkinson's disease (PD). Therefore, the present study was designed to investigate the role of GABA-B receptor modulation in experimental models of MPTP-induced PD. MPTP was administered repeatedly on 1st, 7th and 14th day intranigrally for the induction of PD in Male Wistar rats. Baclofen (10 and 20mg/kg) and GABA-B antagonist CGP35348 (10mg/kg) were given after induction of PD for 14 days. Different behavioural tasks were performed during 1st, 14th, 21st, 28th days after MPTP injection and biochemical parameters were estimated on day 28th. Central administration of MPTP showed significant impairment of motor behaviour and marked increase of oxidative damage LPO and GSH in striatum and cortex. Pro-inflammatory cytokines like TNF-α and IL-ß were significantly increased in striatum region of MPTP treated rats. However, post treatment with baclofen significantly improved the motor abnormalities and attenuated the oxidative damage and neuro-inflammation in MPTP treated rats. CGP35348, GABA-B receptor antagonist, reversed the protective effect of baclofen GABA-B receptor play role in the neuroprotection. The present study concluded that baclofen produce beneficial effect against MPTP induced PD like symptoms rats through GABAergic mechanism.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , Receptores de GABA-B/metabolismo , Animais , Baclofeno/farmacologia , Córtex Cerebral/imunologia , Córtex Cerebral/metabolismo , Corpo Estriado/imunologia , Corpo Estriado/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Agonistas dos Receptores de GABA-B/farmacologia , Antagonistas de Receptores de GABA-B/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/etiologia , Transtornos Parkinsonianos/fisiopatologia , Ratos Wistar , Teste de Desempenho do Rota-Rod
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