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± 1 .14) of 3 groups.-In constantly treated group, the mean number of positive stained neurons was less(3.9+_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 constantly 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
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