An astroglia-linked dopamine D2-receptor action in prefrontal cortex

Zafar U. Khan, Peter Koulen, Marcelo Rubinstein, David Grandy, Patricia S. Goldman-Rakic

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    127 Scopus citations

    Abstract

    Typical neuroleptic drugs elicit their antipsychotic effects mainly by acting as antagonists at dopamine D2 receptors. Much of this activity is thought to occur in the cerebral cortex, where D2 receptors are found largely in inhibitory GABAergic neurons. Here we confirm this localization at the electron microscopic level, but additionally show that a subset of cortical interneurons with low or undetectable expression of D2 receptor isoforms are surrounded by astrocytic processes that strongly express D2 receptors. Ligand binding of isolated astrocyte preparations indicate that cortical astroglia account for approximately one-third of the total D2 receptor binding sites in the cortex, a proportion that we found conserved among rodent, monkey, and human tissues. Further, we show that the D2 receptor-specific agonist, quinpirole, can induce Ca2+ elevation in isolated cortical astrocytes in a pharmacologically reversible manner, thus implicating this receptor in the signaling mechanisms by which astrocytes communicate with each other as well as with neurons. The discovery of D2 receptors in astrocytes with a selective anatomical relationship to interneurons represents a neuron/gila substrate for cortical dopamine action in the adult cerebral cortex and a previously unrecognized site of action for antipsychotic drugs with affinities at the D2 receptor.

    Original languageEnglish (US)
    Pages (from-to)1964-1969
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume98
    Issue number4
    DOIs
    Publication statusPublished - Feb 13 2001

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    ASJC Scopus subject areas

    • Genetics
    • General

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