Interhemispheric modulation of dopamine receptor interactions in unilateral 6‐OHDA rodent model

Cindy P. Lawler, John H. Gilmore, Val J. Watts, Q. David Walker, Stan B. Southerland, Larry L. Cook, Chet A. Mathis, Richard B. Mailman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

A critical assumption in the unilateral 6‐hydroxydopamine (6‐OHDA) model is that interactions between the intact and denervated hemispheres do not influence the response to insult. The present study examined this issue by assessing the effects of unilateral substantia nigra 6‐OHDA lesions in rats that previously had received corpus callosum transections, a treatment designed to minimize interhemispheric influences. Quantitative autoradiography in the caudate‐putamen ipsilateral to the lesion revealed that corpus callosum transection did not alter the increase in D2‐like receptors ([125I]‐epidepride‐labeled sites) that is induced by unilateral 6‐OHDA lesion. There were no effects of either 6‐OHDA lesion or transection on D1 receptor density ([l25I]‐SCH23982 autoradiography). As a functional endpoint, dopamine‐stimulated cAMP efflux was measured in superfused striatal slices. In this paradigm, the net effect of dopamine (DA) represents a combination of D1 receptor‐mediated stimulation and D2 receptor‐mediated inhibition. 6‐OHDA lesion increased cAMP efflux induced by exposure to 100 p.M DA alone; corpus callosum transection did not alter this effect. An interaction between 6‐OHDA lesion and transection status was revealed, however, by comparison of results obtained with DA alone vs. DA plus the D2 antagonist sulpiride (to block the D2 inhibitory effects of 100 p.M DA). This comparison revealed two important effects of 6‐OHDA lesion in rats with an intact corpus callosum: (1)a moderate decrease in dopamine Dl receptor‐mediated stimulation; and (2) a dramatic decrease in the ability of D2 receptors to inhibit this stimulation. Corpus callosum transection prevented these effects of 6‐OHDA. These results provide a biochemical demonstration of D1:D2 receptor uncoupling in unilateral 6‐OHDA lesioned rats, and suggest that interhemispheric influences (e.g., contralateral cortico‐striatal glutamatergic projections) may contribute to lesion‐induced alterations in D1:D2 receptor interactions. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)299-311
Number of pages13
JournalSynapse
Volume21
Issue number4
DOIs
StatePublished - Dec 1995

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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