Nigral dopamine type-1 receptors are reduced in Huntington's disease: a postmortem autoradiographic study using [3H]SCH 23390 and correlation with [3H]forskolin binding.
Intrastriatal injection of excitatory amino acids, particularly quinolinic acid, has been proposed as an animal model of Huntington's disease. Such neurotoxic lesions of caudate-putamen result in marked dopamine type-1 (D1) receptor losses in the injected nuclei as well as in the ipsilateral substantia nigra pars reticulata. Postmortem human substantia nigra from Huntington's disease brains and from control brains were examined using in vitro autoradiography. A marked reduction in [3H]SCH 23390 binding (labeling D1 receptors) in the substantia nigra of postmortem brains of Huntington's patients was identified, thus paralleling the alterations seen in the animal models. A positive, statistically significant correlation was also encountered between D1 receptor binding (labeled by [3H]SCH 23390) and [3H]forskolin binding (which identifies adenylate cyclase, a second messenger system linked to D1 receptor activation). The results suggest that in the human--as in lower vertebrates--D1 receptors are located on striatonigral terminals and that D1 receptor loss tends to be paralleled by a reduction in adenylate cyclase. Radioactive agents selective for the D1 receptor may prove useful in future studies of Huntington's disease using positron emission tomography scanning.
Filloux
F
F
Western Institute of Neuropsychiatry, University of Utah, Salt Lake City 84108.
Wagster
M V
MV
Folstein
S
S
Price
D L
DL
Hedreen
J C
JC
Dawson
T M
TM
Wamsley
J K
JK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000378:metabolism; D002421:Caudate Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D014316:Tritium
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014316:Tritium