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Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons

Nature Neuroscience volume 3, pages 226–230 (2000)Cite this article

Abstract

Despite the importance of dopamine signaling, it remains unknown if the two major subclasses of dopamine receptors exist on the same or distinct populations of neurons. Here we used confocal microscopy to demonstrate that virtually all striatal neurons, both in vitro and in vivo, contained dopamine receptors of both classes. We also provide functional evidence for such colocalization: in essentially all neurons examined, fenoldopam, an agonist of the D1 subclass of receptors, inhibited both the Na+/K+ pump and tetrodotoxin (TTX)-sensitive sodium channels, and quinpirole, an agonist of the D2 subclass of receptors, activated TTX-sensitive sodium channels. Thus D1 and D2 classes of ligands may functionally interact in virtually all dopamine-responsive neurons within the basal ganglia.

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Figure 1: Primary culture of medium spiny neurons from rat embryonic striatum stained for neuronal markers and for D1 and D2 receptors.
Figure 2: D1 and D2 subclasses of receptors colocalize with DARPP-32 in primary cultures and slices of rat neostriatal neurons.
Figure 3: D1-subclass receptors colocalize with D2-subclass receptors in neurons of rat neostriatal slices.
Figure 4: Effects of D1 and D2 agonists and antagonists on initial rates of Na+ influx and efflux in primary cultures of striatal cells.
Figure 5: Effects of D1 and D2 agonists on [Na+]i in primary cultures of rat striatal cells.

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Acknowledgements

We thank Ann-Christine Eklöf for experimental assistance. This work was supported by grants from the Swedish Medical Research Council (H.B. and A.A.), Märta and Gunnar V. Philipsons Foundation (H.B.), NIH grants MH40899 and DA 10044 (P.G.) and a grant from Stiftelsen Frimurare Barnhuset I Stockholm (O.A.).

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  1. Oleg Aizman and Hjalmar Brismar: O.A. and H.B. contributed equally to this work.

Authors and Affiliations

  1. Department of Woman and Child Health, Karolinska Institutet Astrid Lindgren Children's Hospital, Q2:09, Stockholm, 171 76, Sweden

    Oleg Aizman, Hjalmar Brismar, Per Uhlén, Eivor Zettergren, Hans Forssberg & Anita Aperia

  2. Department of Neurology, Emory University School of Medicine Atlanta, Georgia, 30322, Georgia, USA

    Allan I. Levey

  3. Laboratory of Molecular Cellular Neuroscience The Rockefeller University, NewYork, 10021-6399, NewYork, USA

    Paul Greengard

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Correspondence to Anita Aperia.

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Aizman, O., Brismar, H., Uhlén, P. et al. Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons. Nat Neurosci 3, 226–230 (2000). https://doi.org/10.1038/72929

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