Increased [125I]sulpiride binding in the subthalamic nucleus of rats with nigrostriatal lesions.
Subthalamic nucleus (STN) hyperactivity follows lesions of mesencephalic dopaminergic neurons in animal models of Parkinson's disease. The mechanism leading to sustained STN hyperactivity in parkinsonism is not well understood, but it seems not to depend on the integrity of striato-pallido-subthalamic connections (the so called indirect pathway). Sustained STN hyperactivity could result from the loss of the direct dopaminergic innervation of the STN. Here we report increased [125I]sulpiride binding in the STN of rats with 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neurons. Furthermore, we found that chronic oral treatment with levodopa reverted the lesion-induced increase in [125I]sulpiride binding. Our results demonstrate that most STN D2-class dopamine receptors are postsynaptic to afferent dopaminergic fibers. Furthermore, they suggest that alterations of local STN dopaminergic mechanisms could play a role in the pathophysiology of parkinsonism and mediate the therapeutic/adverse effects of chronic levodopa administration.
Murer
M G
MG
Departamento de Fisiología, Facultad de Medicine, Universidad de Buenos Aires, Argentina.
Ferrario
J
J
Delfino
M
M
Dziewczapolski
G
G
Gershanik
O S
OS
Raisman-Vozari
R
R
D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001931:Brain Mapping; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D005260:Female; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000378:metabolism*; D013787:Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism*
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D007980:Levodopa; D013469:Sulpiride; D016627:Oxidopamine; D004298:Dopamine