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Mapping interactions between dopamine and adenosine A2a receptors using pharmacologic MRI.
Y Iris Chen1, Ji-Kyung Choi, Bruce G Jenkins
1MGH-NMR Center and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Synapse (New York, N.Y.)
|November 6, 2004
Summary
Pharmacologic MRI reveals adenosine A2a receptor antagonist DMPX blocks amphetamine-induced dopamine release and blood flow changes in rat basal ganglia. This highlights A2a receptor roles in dopamine regulation.
Area of Science:
- Neuroscience
- Pharmacology
- Neuroimaging
Background:
- Adenosine receptors in the basal ganglia modulate dopamine function.
- Interactions between adenosine and dopamine receptors are crucial for basal ganglia regulation.
Purpose of the Study:
- To investigate the interactions between dopamine and adenosine receptors in the basal ganglia.
- To utilize pharmacologic MRI (phMRI) to study these interactions in vivo.
Main Methods:
- Rats were administered amphetamine to stimulate dopamine receptors.
- The selective A2a receptor antagonist DMPX was used to investigate antagonism of amphetamine-induced changes.
- Relative cerebral blood volume (rCBV) changes were measured using phMRI.
- Microdialysis was used to measure dopamine release.
Main Results:
- Amphetamine increased rCBV in the caudate-putamen (CPu), nucleus accumbens (NAcc), thalamus, and cortical regions.
- DMPX alone decreased rCBV in NAcc, CPu, and olfactory tubercle, consistent with A2a receptor distribution.
- DMPX administration after amphetamine significantly reduced amphetamine-induced rCBV increases in NAcc, CPu, and thalamus.
- DMPX also decreased dopamine release in the CPu.
Conclusions:
- Adenosine A2a receptors play a significant role in modulating dopamine release and associated neurovascular coupling in the basal ganglia.
- Pharmacologic MRI is a valuable tool for noninvasively studying neurotransmitter interactions and their dynamics.