Effects of hypoxic-ischemic brain damage on dopaminergic markers in the neonatal rat: a regional autoradiographic analysis.
Dopamine has been implicated as an endogenous substance that may mediate neuronal death after hypoxic-ischemic insult. Using semiquantitative autoradiography, we studied the effect of perinatal hypoxic-ischemic injury on dopamine binding sites in rat brain. Experimental injury resulted in a substantial decrease in dopamine type-1 (D1) and forskolin (adenylate cyclase) binding sites. In contrast, markers for dopamine type-2 (D2) sites and for dopamine uptake were unaffected in lesioned animals. Changes within dopaminergic pathways were variable, with reduction in binding being encountered mainly in components of the extrapyramidal motor system: caudate-putamen, -61%; globus pallidus, -64%; entopeduncular nucleus, -60%; and substantia nigra, -69%. Furthermore, the topography of D1 receptor loss within the caudate-putamen was not uniform, with the greatest decrement in dorsolateral regions. Reduced D1 versus D2 receptor activation may underlie extrapyramidal movement disorders that appear as a consequence of perinatal hypoxic-ischemic insult.
Adair
J
J
Department of Neurology, University of Utah School of Medicine, Salt Lake City.
Filloux
F
F
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000473:pathology*; D001345:Autoradiography; D001921:Brain / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000473:pathology*; D002547:Cerebral Palsy / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D002534:Hypoxia, Brain / Q000473:pathology*; D007231:Infant, Newborn; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine