파킨슨병 모형 흰쥐의 줄무늬체에서 Apomorphine 투여 방법에 따른 도파민 D2 수용체의 발현

Expression of Dopamine D2 Receptor in Response to Apomorphine Treatment in the Striatum of the Rat with Experimentally Induced Parkinsonism

  • 최승진 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 성재훈 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 손병철 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 박춘근 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 권성오 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 김문찬 (가톨릭대학교 의과대학 신경외과학교실) ;
  • 이상원 (가톨릭대학교 의과대학 신경외과학교실)
  • Choi, Seung Jin (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Sung, Jae Hoon (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Son, Byung Chul (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Park, Choon Keun (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Kwon, Sung Oh (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Kim, Moon Chan (Department of Neurosurgery, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sang Won (Department of Neurosurgery, College of Medicine, The Catholic University of Korea)
  • 투고 : 1999.12.27
  • 심사 : 2000.02.11
  • 발행 : 2000.07.28

초록

Objective : Parkinsonian rat models have generally been characterized by unilateral destruction of both the nigrostriatal pathway and the mesolimbic pathway using the neurotoxin 6-hydroxydopamine. The induction of contraversive turning by apomorphine in these models is thought to reflect the stimulation of supersensitive dopamine D2 receptor or receptor-mediated mechanisms in denervated neostriatum. The present study was undertaken to investigate the expression of dopamine D2 receptor in denervated striatum according to modalities of apomorphine(dopamine agonist) treatment after creating a hemiparkinsonian rat model in which there is 6-hydroxydopamine induced destruction of the unilateral dopaminergic nigrostriatal pathway. Methods : After making complete lesion in left side substantia nigra pars compacta(SNpc) by stereotactic injection of 6-hydroxydopamine into medial and lateral areas of SNpc, and confirming successful animal model by apomorphine induced contraversive turning behavior without recovery and complete destruction of ipsilateral SNpc with tyrosine hydroxylase immunostaining in 7th day after operation, 15 rats of parkinsonian model were studied with or without administration of apomorphine at varying doses and durations. According to the modalities of apomorphine treatment for 4 days, these rats were divided into 3 groups, as not-treated group, intermittently treated group and constantly treated group. For investigating the extent of the expression of dopamine D2 receptor in denervated striatum, immunohistochemical staining by dopamine D2 receptor antibody and Western blot were performed. Results : In the D2 receptor antibody immunohistochemical staining, the mean number of positive stained neurons was highest in not-treated group($20.5{\pm}1.14$) of 3 groups. In constantly treated group, the mean number of positive stained neurons was less($3.9{\pm}1.79$) than intermittently treated group(p<0.05). The Western blotting with the D2 receptor antibody revealed that expression of receptors was also highest in not-treated group and less in constantiy treated group than intermittently treated group. Conclusion : Dopamine D2 receptors in denervated striatum of parkinsonian rat models, which were not treated with apomorphine, revealed to be most highly expressed. And, according to doses and durations of apomorphine administration, desensitization of the receptor was more apt to develop with constant treatment than intermittent treatment. In clinical setting, the authors believe that, in long-term treated parkinsonian patients, desensitization of dopamine receptors due to chronic dopaminergic stimulation seems to be partially related to mechanisms of drug tolerance.

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