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An astroglia-linked dopamine D2-receptor action in prefrontal cortex
Z U Khan1, P Koulen, M Rubinstein
1Section of Neurobiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8001, USA. zkhan@kafka.med.yale.edu
Summary
Dopamine D2 receptors, crucial for antipsychotic drugs, are found in brain astrocytes, not just neurons. This discovery reveals a new target for treating psychosis in the cerebral cortex.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Antipsychotic drugs primarily target dopamine D2 receptors for therapeutic effects.
- Dopamine D2 receptors were traditionally localized to GABAergic neurons in the cerebral cortex.
Purpose of the Study:
- To investigate the precise localization of dopamine D2 receptors in the adult cerebral cortex.
- To explore the functional role of D2 receptors in astrocytes and their interaction with neurons.
Main Methods:
- Electron microscopy to confirm receptor localization.
- Ligand binding assays on isolated astrocyte preparations.
- Pharmacological stimulation with D2 receptor agonist quinpirole to induce calcium elevation in astrocytes.
Main Results:
- Dopamine D2 receptors are expressed in astrocytic processes surrounding a subset of cortical interneurons.
- Astrocytes account for approximately one-third of cortical D2 receptor binding sites across species.
- D2 receptor activation in astrocytes triggers a calcium signaling response, indicating a role in cell communication.
Conclusions:
- Astrocytes represent a significant, previously unrecognized site for dopamine D2 receptor action in the cerebral cortex.
- This neuron-glia interaction provides a novel substrate for dopamine signaling and a potential new target for antipsychotic drug development.