Study of dopamine transporter in the rat 6-hydroxydopamine Parkinson's disease model

J Korean Neurol Assoc > Volume 16(4); 1998 > Article

Journal of the Korean Neurological Association 1998;16(4): 536-546.

6-Hydroxydopamine을 이용한 파킨슨병 흰쥐 모델에서 도파민 운반체의 변화

김상윤, 정 재 민*. 장 영 수*. 주 완 석**. 맹 성 호**. 하 충 건**** 김 종 민***. 김 용 식**. 이 명 철*. 이 상 복***. 전 범 석**

한림대학교 의과대학 신경과학교실 서울대학교 의과대학 핵의학과교실* 약리학교실** 신경과학교실*** 인하대학교 의과대학 신경과학교실****

Study of dopamine transporter in the rat 6-hydroxydopamine Parkinson's disease model

Sang-Yun Kim . Jae-Min Jung* . Young-Soo Chang* . Wan Seok Joo** Sung Ho Maeng** . Chung-Gun Ha**** . Jong-Min Kim*** Yong Sik Kim** . Myung-Chul Lee* . Sang-Bok Lee*** . Beom S Jeon***

Department of Neurology Hallym University College of Medicine Departments of Nuclear Medicine*, Pharmacology**, and Neurology*** Seoul National University College of Medicine Department of Neurology Inha University College of Medicine****

Abstract

Background : Neuroprotective therapy is essential in the management of Parkinson's disease(PD). As symptomatic benefit of a treatment may clinically mask the disease progression, an evaluation of the effect of a neuroprotective therapy should be based on objective measurement of in vivo dopaminergic integrity: Nuclear imaging techniques such as SPECT or PET can visualize dopaminergic system using dopamine transporter ligands and show the promise for this purpose. The objective of this study is to examine the changes of dopamine transporter in the animal model of PD and those correlations with behavioral and biochemical changes. Methods : We injected 6-hydroxydopamine into the substantia nigra in Sprague-Dawley rats to establish the unilateral PD model, and examined the rotation response after apomorphine injection as a behavioral aspect of the animal model. And we also measured the dopamine and DOPAC level in the striata and the dopamine transporter by [3H]-mazindol autoradiography. Results : We observed that the rats showed turning behavior only after severe reduction of dopamine and DOPAC. There was a strong inverse correlation between rotation behavior and striatal dopamine, DOPAC and dopamine transporter density. There was a positive and strong linear-correlation between dopamine transporter density and dopamine or DOPAC levels. Conclusion : Measurement of dopamine transporter gives a good estimate of striatal dopamine level in an animal model of PD. In vivo measurement of dopamine transporter will give an objective information on the integrity of presynaptic nigrostriatal dopaminergic system. Key Words : Dopamine transporter, Parkinson's disease, 6-Hydroxydopamine, Mazindol, Dopamine, DOPAC