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Upregulation of the NR1 mRNA in the subthalamic nucleus of 6-hydroxydopamine lesioned-rats treated withl-DOPA

Authors
Journal
International Congress Series
0531-5131
Publisher
Elsevier
Publication Date
Volume
1251
Identifiers
DOI: 10.1016/s0531-5131(03)00109-2
Keywords
  • Nmda Receptor
  • Glutamate Receptor
  • Levodopa
  • Dyskinesias
  • Parkinson'S Disease
Disciplines
  • Medicine

Abstract

Abstract In rats with unilateral lesions of the nigrostriatal dopamine pathway with 6-hydroxydopamine (6-OHDA), the motor stimulating effects of l-DOPA, evidenced by rotation behavior, become enhanced on repeated administration. However, the mechanisms of this behavioral sensitization to l-DOPA, that is an analogue to l-DOPA-induced dyskinesias (LID) in patients with Parkinson's disease, remain unknown. It has been suggested that alterations of glutamatergic afferents to the subthalamic nucleus (STN) are implicated in the development of LID. To determine the relevance of glutamatergic dysfunctions in the STN to the development of LID, we analyzed the expression of mRNAs coding for N-methyl- d-aspartate (NMDA) receptor subunits, NR1/2A/2B/2C, in the STN of 6-OHDA-lesioned rats treated with l-DOPA twice daily for 2 weeks. These rats showed marked behavioral sensitization to l-DOPA. The expression of the NR1 mRNA was significantly increased in the lesioned-side STN of the sensitized 6-OHDA rats. This result suggests that alterations of glutamatergic drives to the STN are involved in the development of LID.

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