The Effects of Dopamin D-1 Agonist (SKF-38393) on Expression of Substance-P & Enkephalin mRNA in the Striatum of Hemiparkinsonian Rat Model

ABSTRACT

BACKGROUND: The selective D1 dopamine agonist has been known to play a stimulatory role in substance-P synthesis in the striatum, but its effect on the enkephalin mRNA expression has not been well known in the striatum of unilateral 6-hydroxydopamine(OHDA)-lesioned rat. So we investigated the effect of selective D1 dopaminergic agonist on substance-P, enkephalin mRNA expression in the striatum with different time interval. METHODS: The lesioned rats were divided into two groups (treated and non-treated). Each group was subdivided according to time course after lesioning (2nd, 4th and 8th week). Dopamine 1 receptor agonist, SKF-38393 (5 mg/kg/ip) and the same volume of saline was injected to treated and nontreated group respectively. The levels of enkephalin and substance-P mRNA were determined by in situ-hydridization and the expression of mRNA levels were compared between the groups. RESULTS: The expression of striatal enkephalin mRNA was increased on lesioned side in all groups. Especially, SKF-38393 enhanced the striatal expression of enkephalin mRNA after lesioning 2nd week. After lesioning 4th week and 8th week, the effect of SKF-38393 was not significant. The striatal expression of substance-P mRNAs was significantly decreased on the lesioned side, especially at the 2nd weeks. This decrement of substance-P mRNA was reversed by SKF-38393 at the 2nd week. CONCLUSIONS: These data show that the selective D1 agonist SKF-38393 have an agonistic effect on direct pathway but antagonistic effect on indirect pathway in early course of Parkinsonian rat model.