Abstract:

Abstract:Objective To study the  effects of benserazide on extracellular dopamine level in the striatum of 6-hydroxydopamine- lesioned Parkinson’s disease rat models. Methods The rat models of nigrostriatal denervation of Parkinson's disease were set up by using 6-hydroxydopamine (6-OHDA)，and the control rats were treated with isotonic Na chloride. Then the extracellular dopamine(DA) level in the striatum of sham-lesioned rats treated with benserazide alone and in the striatum of 6-OHDA-lesioned rats treated with benserazide in combination with L-DOPA were detected by using in vivo microdialysis technique. Results In sham-lesioned rats, the extracellular DA level was significantly decreased by  50  mg?kg-1benserazide（P<0.01）.  In 6-OHDA-lesioned rats,the  extracellular DA level showed a marked increase by the combined use of benserazide and L-DOPA, but the time to reach the peak level was significantly prolonged on a dose-dependent manner（P<0.05）. Conclusion Benserazide can reduce the central AADC activity in the striatum of rats with nigrostriatal denervation, resulting in changes in metabolism of exogenous L-DOPA. And  higher dose of benserazide might be a useful agent to prevent adverse effects of long-term L-DOPA therapy.

Key words: benserazide, L-DOPA, dopamine, animal model, microdialysis, aromatic L-amino acid decarboxylase