Temporal changes of dopaminergic and glutamatergic receptors in 6- hydroxydopamine-treated rat brain

Tsutomu Araki, Hiroaki Tanji, Hiroyuki Kato, Yutaka Imai, Michinao Mizugaki, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Quantitative receptor autoradiography was used to examine the sequential patterns of changes in dopaminergic and glutamatergic receptors in the brain of rats lesioned with 6-hydroxydopamine. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks of postlesion. Degeneration of the nigrostriatal pathway caused a significant increase in dopamine D2 receptors in the ipsilateral striatum from 1 to 8 weeks of postlesion. In the ipsilateral substantia nigra (SN), a significant decrease in dopamine D2 receptors was also observed from 1 to 8 weeks of postlesion. On the other hand, dopamine D1 receptors were increased in the ipsilateral ventromedial striatum from 2 to 4 weeks of postlesion. In the ipsilateral SN, a transient increase in dopamine D1 receptors was observed only 1 week after lesioning. However, other regions in both ipsilateral and contralateral sides showed no significant change in dopamine D1 and D2 receptors during postlesion except for a transient change in a few regions. N-Methyl-D-aspartate (NMDA) receptors showed no significant changes in all brain regions studied during the postlesion. In contrast, a transient increase in excitatory amino acid transport sites was observed only in the frontal cortex and ventromedial striatum of the ipsilateral side at 2 weeks of postlesion. However, glycine receptors showed a significant change in any brain areas of both ipsilateral and contralateral sides after lesioning. The change in the brain areas of contralateral side was more pronounced than that of ipsilateral side for glycine receptors. In addition, dopamine uptake sites showed a severe damage in the ipsilateral striatum from 1 to 8 weeks after lesioning. In the contralateral side, in contrast, no significant change in dopamine uptake sites was found in the striatum during the postlesion. These results indicate that unilateral injection of 6- hydroxydopamine in the medial forebrain bundle can cause a significant increase in dopamine D1 and D2 receptors in the striatum. The increase in dopamine D2 receptors was more pronounced than that in dopamine D1 receptors in the striatum after 6-hydroxydopamine treatment. In contrast, dopamine uptake sites showed a severe damage in the striatum during the postlesion. Furthermore, our results support the existence of dopamine D2 receptors on the neurons of SN, but not dopamine D1 receptors. For glutamatergic receptor system, the present study suggests that the changes in glycine receptors may be more susceptible to degeneration of nigrostriatal pathway than NMDA receptors and excitatory amino acid transport sites. Thus, our findings are of interest in relation of degeneration of the nigrostriatal pathway that occurs in Parkinson's disease (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)365-375
Number of pages11
JournalEuropean Neuropsychopharmacology
Volume10
Issue number5
DOIs
Publication statusPublished - 2000 Sep

Keywords

  • 6- Hydroxydopamine
  • Dopamine receptors
  • Dopamine uptake sites
  • Excitatory amino acid transport sites
  • Glycine binding sites
  • NMDA receptors
  • Nigrostriatal pathway
  • Rats
  • Receptor autoradiography

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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