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.

Abstract:

: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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Filloux F,Wagster MV,Folstein S,Price DL,Hedreen JC,Dawson TM,Wamsley JK

doi

10.1016/0014-4886(90)90033-o

subject

Has Abstract

pub_date

1990-11-01 00:00:00

pages

219-27

issue

2

eissn

0014-4886

issn

1090-2430

pii

0014-4886(90)90033-O

journal_volume

110

pub_type

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