Mapping interactions between dopamine and adenosine A2a receptors using pharmacologic MRI.
Adenosine receptors in the basal ganglia are implicated in regulation of dopamine function and release. We investigated the interactions between dopamine receptors and adenosine receptors in the basal ganglia using pharmacologic MRI (phMRI) in rats. Stimulation of dopamine receptors was achieved using administration of 2 mg/kg of amphetamine. Then we investigated the antagonism of these changes using the selective A2a receptor antagonist 3,7-dimethyl-1-propargylaxanthine (DMPX). Amphetamine alone caused large increases (10-30%) in relative cerebral blood volume (rCBV) in caudate/putamen (CPu), nucleus accumbens (NAcc), thalamus, and frontal and cingulate cortices with changes that persisted for 70-80 min. DMPX alone (5 mg/kg) induced decreases in rCBV (approximately 8-10%) in NAcc, CPu, and olfactory tubercule, with smaller changes in thalamus (-6%) consistent with the regional distribution of A2a receptors. We examined the interactions between amphetamine and DMPX by assessing the effects of DMPX (5 mg/kg) administration 20 min after injection of 3 mg/kg amphetamine. These experiments showed that DMPX immediately decreased the rCBV increase induced by amphetamine in NAcc, CPu, and thalamus but not in cingulate or sensorimotor cortex. Companion microdialysis experiments showed that dopamine release in CPu was decreased in a similar manner. These experiments demonstrate the utility of phMRI for probing, in a noninvasive manner, the temporal and spatial dynamics of neurotransmitter interactions.
Chen
Y Iris
YI
MGH-NMR Center and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Choi
Ji-Kyung
JK
Jenkins
Bruce G
BG
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D058917:Adenosine A2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; C057837:3,7-dimethyl-1-propargylxanthine; D013805:Theobromine; D003913:Dextroamphetamine; D004298:Dopamine