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The Journal of Neuroscience, September 1, 2000, 20(17):6666-6671

Dopamine D₁ Receptors Synergize with D₂, But Not D₃ or D₄, Receptors in the Striatum without the Involvement of Action Potentials

Gerald J. LaHoste¹, Brook L. Henry², and John F. Marshall²

¹ Department of Psychology, University of New Orleans, New Orleans, Louisiana 70148, and ² Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697

The widespread biological actions of the neurotransmitter dopamine (DA) are mediated by two classes of receptor, the D₁ class (D₁ and D₅) and the D₂ class (D₂, D₃, and D₄), which interact synergistically in many paradigms, such as DA agonist-stimulated motor behavior and striatal c-fos expression. Understanding the mechanism(s) of this interaction has been impeded by a controversy regarding the cellular localization of D₁ and D₂ class receptors. To address this issue from a functional point of view, we elicited striatal Fos by combined administration of a D₁ class and a D₂ class agonist either in the presence or absence of the fast sodium channel blocker tetrodotoxin (TTX). Striatal Fos elicited by direct D₁/D₂ stimulation was not reduced by TTX. By contrast, TTX greatly attenuated the Fos response evoked by cocaine or GBR 12909. In separate experiments using antagonists that distinguish among members of the D₂ class of receptors, amphetamine-stimulated Fos and motor behavior were attenuated dose-dependently by the selective D₂ antagonist L-741,626, but not by the selective D₃ antagonist U99194A or the D₄-selective antagonist L-745,870. Because Fos expression in the paradigms that were used occurs in enkephalin-negative striatonigral neurons, which show limited coexpression of D₁ and D₂ receptors, the present findings taken together suggest the intriguing possibility that D₁/D₂ synergism may be mediated by D₁ and D₂ receptors residing on separate striatal neurons and interacting in a manner that is not dependent on action potentials.

Key words: D₁ receptors; D₂ receptors; D₁/D₂ synergism; D₃ receptors; D₄ receptors; tetrodotoxin; amphetamine; motor behavior; Fos; striatum

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20176666-06$05.00/0

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