Effect of unilateral perinatal hypoxic-ischemic brain injury in the rat on dopamine D1 and D2 receptors and uptake sites: a quantitative autoradiographic study.
The effect of a unilateral perinatal hypoxic-ischemic brain injury on dopamine D1 and D2 receptors and uptake sites was investigated in rats by using in vitro quantitative binding autoradiography, 2-3 weeks after the insult. We observed significant decreases in the Bmax and KD for [3H]SCH 23390-labeled D1 and in the Bmax for [3H]spiperone-labeled D2 receptors in the lesioned caudate-putamen in rats with moderate brain injury (visible loss in hemispheric volume ipsilateral to the injury) compared with the nonlesioned contralateral caudate-putamen or with control rats. Changes in [3H]SCH 23390 and [3H]spiperone binding predominated in the dorsolateral part of the lesioned caudate-putamen. Pronounced reduction in [3H]SCH 23390 binding was also observed in the substantia nigra pars reticulata on the side of the lesion. In contrast, we did not observe any significant change in Bmax or KD for [3H]mazindol-labeled dopamine uptake sites. Similarly, no significant changes in the levels of dopamine or its metabolites were found on the side of the lesion. The observed reductions in striatal dopamine D1 and D2 receptors are a reflection of striatal cell loss induced by the hypoxic-ischemic injury. The absence of changes in [3H]mazindol binding or dopamine levels in the lesioned caudate-putamen indicates that the dopaminergic presynaptic structures are preserved.
Przedborski
S
S
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Kostic
V
V
Jackson-Lewis
V
V
Cadet
J L
JL
Burke
R E
RE
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D001679:Biogenic Amines / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008454:Mazindol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D001679:Biogenic Amines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D008454:Mazindol