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% O-2 for 3 h). Controls underwent sham surgery alone. Animals surviving for 2-80 days following HI were studied. Striatal D-1 receptors (labeled by [H-3]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). D-2 receptors (labeled by [I-125]iodosulpride) did not decline until 10 days after HI, and remained uniformly depressed throughout the caudate-putamen thereafter. Changes in D-1 receptor mRNA transcripts closely paralleled alterations in receptors: early reductions in D-1 mRNA signal recovered by young adulthood. D-2 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 D-1 receptor expression recovers from neonatal HI injury, D-2 receptors remain permanently affected despite the presence of normal levels of D-2 receptor transcripts. A persistent, post-transcriptional effect of HI on D-2 receptor expression is suggested.