Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging.
BACKGROUND
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.
Chen
Yin-Ching I
YC
Athinoula A. Martinos Center for Biomedical Imaging and MGH-NMR Center, Department of Radiology Massachusetts General Hospital, Charlestown, MA 02129, USA.
Choi
Ji-Kyung
JK
Andersen
Susan L
SL
Rosen
Bruce R
BR
Jenkins
Bruce G
BG
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000098:blood supply* / Q000187:drug effects; D001931:Brain Mapping; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005290:Ferric Compounds / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005290:Ferric Compounds; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C000499:ferric oxide; D019257:Quinpirole; D000661:Amphetamine; C045989:eticlopride; D010100:Oxygen