Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain.
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 D(2) receptors in the ipsilateral striatum from 1 to 8 weeks of postlesion. In the ipsilateral substantia nigra (SN), a significant decrease in dopamine D(2) receptors was also observed from 1 to 8 weeks of postlesion. On the other hand, dopamine D(1) receptors were increased in the ipsilateral ventromedial striatum from 2 to 4 weeks of postlesion. In the ipsilateral SN, a transient increase in dopamine D(1) receptors was observed only 1 week after lesioning. However, other regions in both ipsilateral and contralateral sides showed no significant change in dopamine D(1) and D(2) 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 D(1) and D(2) receptors in the striatum. The increase in dopamine D(2) receptors was more pronounced than that in dopamine D(1) 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 D(2) receptors on the neurons of SN, but not dopamine D(1) 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
Araki
T
T
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Aoba-yama, Sendai 980-8578, Japan. tsuaraki@mail.cc.tohoku.ac.jp
Tanji
H
H
Kato
H
H
Imai
Y
Y
Mizugaki
M
M
Itoyama
Y
Y
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D007839:Functional Laterality; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D016627:Oxidopamine; D004298:Dopamine