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Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging

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Abstract

Rationale

Regulation of dopamine release and synthesis occurs via pre-synaptic dopamine (DA) D2/D3 autoreceptors (DARs). Mapping of DAR function in vivo is difficult and is usually best assessed using invasive measures of DA release, such as microdialysis at discrete sites. We wished to show that pharmacological magnetic resonance imaging (phMRI) may prove useful for this purpose.

Objective

To demonstrate that the relative cerebral blood volume (rCBV) changes induced by amphetamine can be modulated by DA D2 receptor antagonists and agonists in a manner consistent with modulation of DAR function and to compare these effects with microdialysis.

Methods

We used phMRI with iron oxide contrast agents to map changes in rCBV in response to an amphetamine challenge, pre-treatment and post-treatment with varying doses of the D2 antagonist eticlopride and the D2 agonist quinpirole. We also compared the effects of D2 antagonism using microdialysis measurements of DA release.

Results

Antagonism of D2 receptors with eticlopride potentiated rCBV changes induced by amphetamine in the nucleus accumbens and caudate putamen in a dose-dependent manner. The amphetamine-induced increase in rCBV in the accumbens in animals pre-treated with eticlopride was paralleled by a similar percentage increase in DA release measured by means of microdialysis. Conversely, agonism of D2 receptors using quinpirole reduced amphetamine-induced rCBV changes in the caudate putamen and nucleus accumbens. The effects of both quinpirole and eticlopride on amphetamine-induced rCBV changes were largest in the nucleus accumbens.

Conclusions

These results suggest that phMRI may potentially prove useful to map DAR function non-invasively in multiple brain regions simultaneously.

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Acknowledgements

This work is supported in part by NIH NIDA:RO1 DA16187, NIH NIDA 5PO1DA09467 and the Office of National Drug Control Policy CTAC program.

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Authors and Affiliations

  1. Athinoula A. Martinos Center for Biomedical Imaging and MGH-NMR Center, Department of Radiology Massachusetts General Hospital, Charlestown, MA 02129, USA

    Yin-Ching I. Chen, Ji-Kyung Choi, Bruce R. Rosen & Bruce G. Jenkins

  2. Department of Psychiatry, McLean Hospital, Belmont, MA 02478, USA

    Susan L. Andersen

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  1. Yin-Ching I. Chen
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  2. Ji-Kyung Choi
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  3. Susan L. Andersen
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  4. Bruce R. Rosen
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  5. Bruce G. Jenkins
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Correspondence to Bruce G. Jenkins.

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Chen, YC.I., Choi, JK., Andersen, S.L. et al. Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging. Psychopharmacology 180, 705–715 (2005). https://doi.org/10.1007/s00213-004-2034-0

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  • DOI: https://doi.org/10.1007/s00213-004-2034-0

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