[Effects of chronic, systemic treatment with metabotropic glutamate receptor 5 antagonist on behavioral activity and neuroprotection in a preclinical rat model of Parkinson's disease].
[Effects of chronic, systemic treatment with metabotropic glutamate receptor 5 antagonist on behavioral activity and neuroprotection in a preclinical rat model of Parkinson's disease].
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Original abstract
OBJECTIVE: To study the effects of chronic, systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on behavioral activity and neuroprotection in the rat with partial lesion of the nigrostriatal pathway. METHODS: A total of 37 male SD rats were randomly divided into sham (n=11), PD+ saline (n=15) and PD+MPEP group (n=11). Rat model of Parkinson's disease was established by injection of 6-OHDA into medial forebrain bundle. PD+vehicle rats and PD+MPEP rats were injected with NS (0.1 mL) and MPEP (3 mg/kg) per day respectively. Changes in the spontaneous and induced behaviors and the degree of dopamimnergic neurons loss in the substantia nigra pars compacta (SNpc) were observed by behavioral and immunocytochemical methods in partially lesioned and MPEP-treated rats. RESULTS: Unilateral injection of 6-hydrodopamine (6-OHDA) into medial forebrain bundle resulted in the moderate loss (39%) of dopaminergic neurons in the SNpc, and MPEP treatment decreased the number of neurons loss compared with PD+saline rats (P < 0.01). In this model, the lesioned rats did not show obviously abnormal posture. However, apomorphine (APO) induced significant rotation behavior, which increases in a time-dependent manner. Chronic, systemic treatment with MPEP could against the toxicity of 6-OHDA, and reduced the loss of SNpc dopaminergic neurons. In addition, MPEP ameliorated significantly the rotation behaviour induced by APO, which is strengthened in a time-dependent manner. CONCLUSION: MPEP treatment has anti-parkinsonian and neuroprotective effects in the rat with partial lesion of the nigrostriatal pathway, and the efficacy gradually increase with the treatment time.