Roles of dopamine and its receptors in generation of choreic movements.
We have recently succeeded in reproducing choreic movements in the monkey by creating a kainic acid lesion in part of the striatum and by administration of L-DOPA. Based on the morphological and biochemical analyses of monkey brains, we propose that the mechanism of choreic movements is the presynaptic "activation" of the nigrostriatal dopaminergic pathways rather than the postsynaptic receptor activation, especially in the putamen. The important role of the putamen in the generation of choreic movements was clearly supported by the electro-physiological study on this model. Moreover, the activation of the presynaptic dopaminergic nerve terminals in and around the lesioned area was demonstrated by autoradiographs for 2DG uptake. This hypothesis coincides well with the clinical and clinicopharmacological experience in Huntington's disease.
Kanazawa
I
I
Department of Neurology, University of Tokyo, Japan.
Murata
M
M
Kimura
M
M
D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000502:physiology; D002819:Chorea / Q000139:chemically induced / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008251:Macaca; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D013134:Spiperone / Q000493:pharmacokinetics; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005971:Glutamates; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; D007980:Levodopa; D013134:Spiperone; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D007608:Kainic Acid; D004298:Dopamine