The temporal evolution of striatal dopamine receptor binding and mRNA expression following hypoxia-ischemia in the neonatal rat.
Neonatal hypoxic-ischemic (HI) brain injury in the rat alters dopamine receptors. To determine whether such changes are permanent, dopamine receptors and corresponding mRNA were examined at various time points after neonatal HI using receptor autoradiography and in situ hybridization. Rat pups underwent ligation of the left common carotid artery followed by hypoxic exposure (8.5% O2 for 3 h). Controls underwent sham surgery alone. Animals surviving for 2-80 days following HI were studied. Striatal D1 receptors (labeled by [3H]SCH23390) were reduced as early as 2 days following HI, remained depressed for 21 days, but recovered to control levels by young adulthood (3 months of age). D2 receptors (labeled by [125I] iodosulpride) did not decline until 10 days after HI, and remained uniformly depressed throughout the caudate-putamen thereafter. Changes in D1 receptor mRNA transcripts closely paralleled alterations in receptors: early reductions in D1 mRNA signal recovered by young adulthood. D2 mRNA exhibited a unique temporal profile with an early decrease (2 days following HI), and prompt, persistent recovery. Dopamine receptors and transcripts are differentially affected by HI injury early in development. Whereas D1 receptor expression recovers from neonatal HI injury, D2 receptors remain permanently affected despite the presence of normal levels of D2 receptor transcripts. A persistent, post-transcriptional effect of HI on D2 receptor expression is suggested.
Filloux
F M
FM
Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, USA. francis.filloux@m.cc.utah.edu
Adair
J
J
Narang
N
N
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001483:Base Sequence; D001552:Benzazepines / Q000494:pharmacology; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D002534:Hypoxia, Brain / Q000235:genetics / Q000503:physiopathology*; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000737:chemistry* / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C045105:iodosulpride; D014316:Tritium; D013469:Sulpiride