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일측성선조체의 6-OHDA손상 후 도파민효능약물 투여로 발현된 회전운동의 특성
이순철,문민선,이수정,유민,윤철호,유관희 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-
The present study examined the characteristics of behavior induced by dopamine agonists following treatment with 6-hydroxydopamine(6-OHDA) unilaterally into left striatum in rats. 6-OHDA was administered at doses of 8.16 and 24 ㎍/2㎕(in 0.1% ascorbic acid) into dopaminergic neurons in left striatum of 7 weeks old rat under anesthetic. Locomotor activity was significantly decreased at 1 week following 6-OHDA-administration in 7 weeks old rats. The contralateral circling behaviour was inducd by apomorphine(5 ㎎/㎏, I.p.) after 1 week following 6-OHDA(24 ㎍/2㎕) treatment, and was further increased by repeated administration of apomorphine at 2, 3 and 4 weeks. The contralateral circling behavior was also induced by lisuride and 1-dopa in a dose dependent manner, but not by SK & F 82526 in 7 weeks old rats treated with 6-OHDA, The contralteral circling behavior ws significantly higher in 21 weeks old rats but significantly lower in 35 weeks old rats when compared with 7 weeks old rats. The contralateral circling behavior induced by apomorphine did not differ significantly in and 35 weeks old male and female rats. These results suggest that 6-OHDA treatment into left striatum causes remarkable destruction of intrastriatal dopaminergic neurons leading to dopaminergic receptor supersensitivity. Thus, the contralateral circling behavior induced by apomorphine may be used as indicator for neurodegenerative diseases.
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HPLC-ECD를 이용한 흰쥐 뇌의 선조체 중 신경전달물질의 동시분석시 최적 조건
강종성,문민선,신형선,이순철 충남대학교 약학대학 의약품개발연구소 1995 藥學論文集 Vol.11 No.-
흰쥐 뇌의 선조체로부터 catecholamine, indoleamine 및 대사산물을 동시분석할 수 있는 간편한 방법을 제시하였다. 기기는 ECD를 장착한 HPCL를 사용하였고, 고정상인 C_18 컬럼에서, 이동상은 10mM citric acid, 0.13mM Na_4EDTA, 0.58mM SOS를 함유하는 35mM sodium acetate buffer(pH 3.4) : MeOH=85:15가 최적이었다. 이 때 컬럼온도는 30℃였다. 이 조건으로 dopamine(DA), 3, 4 -dihydroxyphenyl acetic acid(DOPAC), homovanilic acid(HVA), 5-hydroxyindole acetic acid(5-HIAA), serotonin(5-HT) 및 noradrenaline(NA)을 미량까지 분석할 수 있었고, 검출한계는 각 성분에 대해 1회 주입당 2~10pg이었다. 이 방법으로 흰쥐의 주령 및 성별에 따른 선조체내 생체아민과 대사산물의 함량을 비교하였다. 7주령 쥐에서 암컷은 수컷보다 DA와 5-HT의 함량이 유의성 있게 높은 것으로 나타났으며, 주령이 증가함에 따라 암컷에서 DOPAC의 함량이 유의적으로 증가하였다. A simple, efficient and sensitive method was described for the simultaneous determination of catecholamine, indoleamine and related metabolites from the homogenates of the rat brain striatum by HPLC-ECD. The optimum mobile phase on a reverse phase C_18 column was 35mM sodium acetate buffer(included 10mM citric acid, 0.13mM Na_4EDTA, 0.58mM SOS, pH 3·4):MeOH=85:15. The column temperature was 30℃. Dopamine(DA), 3, 4-dihydroxyphenyl acetic acid(DOPAC), homovanilic acid(HVA), 5-hydroxyindole acetic acid(5-HIAA), serotonin(5-HT) and noradrenaline(NA) could be separated and analysed to very small amount. The detection limits of this method were 2~10pg per injection for all components. The effects of age and sex of rat on the contents of the catecholamines and their metabolites in rat brain striatum were studied. The levels of DA and 5-HT contents of the 7 week old female rats were higher than those of the 7 week old male rats. As the age of rat increases, the contents of DOPAC increased significantly.
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