THE TEMPORAL EVOLUTION OF STRIATAL DOPAMINE-RECEPTOR BINDING AND MESSENGER-RNA 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 hybridiza tion. Rat pups underwent ligation of the left common carotid artery fo llowed by hypoxic exposure (8.5% O-2 for 3 h). Controls underwent sham surgery alone. Animals surviving for 2-80 days following HI were stud ied. Striatal D-1 receptors (labeled by [H-3]SCH23390) were reduced as early as 2 days following HI, remained depressed for 21 days, but rec overed to control levels by young adulthood (3 months of age). D-2 rec eptors (labeled by [I-125]iodosulpride) did not decline until 10 days after HI, and remained uniformly depressed throughout the caudate-puta men thereafter. Changes in D-1 receptor mRNA transcripts closely paral leled alterations in receptors: early reductions in D-1 mRNA signal re covered by young adulthood. D-2 mRNA exhibited a unique temporal profi le with an early decrease (2 days following HI), and prompt, persisten t recovery. Dopamine receptors and transcripts are differentially affe cted by HI injury early in development. Whereas D-1 receptor expressio n recovers from neonatal HI injury, D-2 receptors remain permanently a ffected despite the presence of normal levels of D-2 receptor transcri pts. A persistent, post-transcriptional effect of HI on D-2 receptor e xpression is suggested.