Mapping dopamine function in primates using pharmacologic magnetic resonance imaging.
Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry in nonhuman primates with high sensitivity and spatial resolution. Seven control cynomolgous monkeys and 10 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied longitudinally using both positron emission tomography (PET) and phMRI. Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative cerebral blood volume (rCBV) in a number of brain regions not described previously, such as parafascicular thalamus, precentral gyrus, and dentate nucleus of the cerebellum. With the high spatial resolution, we were also able to readily identify changes in rCBV in the anterior cingulate, substantia nigra, ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens. Amphetamine induced decreases in rCBV in occipital and posterior parietal cortices. Parkinsonian primates had a prominent loss of response to amphetamine, with relative sparing of the nucleus accumbens and parafascicular thalamus. There was a significant correlation between rCBV loss in the substantia nigra and both PET imaging of dopamine transporters and behavioral measures. Monkeys with partial lesions as defined by 2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane binding to dopamine transporters showed recruitment of premotor and motor cortex after amphetamine stimulus similar to what has been noted in Parkinson's patients during motor tasks. These data indicate that phMRI is a powerful tool for assessment of dynamic changes associated with normal and dysfunctional DA brain circuitry in primates.
Jenkins
Bruce G
BG
Massachusetts General Hospital (MGH) Nuclear Magnetic Resonance Center, Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts 02129, USA.
Sanchez-Pernaute
Rosario
R
Brownell
Anna-Liisa
AL
Chen
Yin-Ching Iris
YC
Isacson
Ole
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D011869:Radioligand Assay
D015259:Dopamine Agents; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine