Augmented sensitivity of D1-dopamine receptors in lateral but not medial striatum after 6-hydroxydopamine-induced lesions in the neonatal rat

PE Simson, KB Johnson, HA Jurevics, HE Criswell, TC Napier, GE Duncan, RA Mueller and GR Breese

Department of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill.

Lesioning of neonatal rats with the neurotoxin 6-hydroxydopamine (6- OHDA) reduced striatal dopamine (DA) levels to 3% of control levels and produced marked increases in the behavioral effects of the selective D1- DA receptor agonist SKF-38393 in these animals when tested as adults. However, no differences were observed, either in basal or D1-DA- stimulated striatal cAMP formation or in forskolin-stimulated or GTP- stimulated cAMP production, between control and lesioned animals. C-fos- like immunoreactivity after SKF-38393 was significantly greater in dorsolateral vs. ventromedial aspects of the striatum in lesioned animals. Like the c-fos response, augmented electrophysiological responsiveness to SKF-38393 occurred in lesioned rats in lateral, but not medial, portions of the striatum. No differences were found in nucleus accumbens in sensitivity to SKF-38393 between control and lesioned rats. Although autoradiographic determination of D1-DA receptor binding throughout the striatum and nucleus accumbens revealed no differences between unlesioned and lesioned rats, tyrosine hydroxylase-like immunoreactivity was reduced with a regional distribution inversely related to c-fos-like immunohistochemical expression. These findings demonstrate that regionally enhanced electrophysiological sensitivity of striatal neurons to D1-DA receptor agonists after neonatal 6-OHDA-induced lesions is associated with regional changes in c-fos-like immunoreactivity and tyrosine hydroxylase-like immunohistochemistry, but not with changes in D1-DA receptor autoradiography or D1-DA-stimulated adenylyl cyclase activity. Such regional consequences of 6-OHDA-induced lesions in neonates may contribute to the unique behavioral patterns observed when these rats are challenged with L-dopa or D1-DA agonists as adults.

Volume 263, Issue 3, pp. 1454-1463, 12/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics

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