Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 43, Pages 9553-9560Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1558-04.2004
Keywords
amphetamine; dopamine; MRI; macaque; Parkinson's disease; PET
Categories
Funding
- NCRR NIH HHS [P51 RR000168, P51RR00168] Funding Source: Medline
- NIDA NIH HHS [DA-09467, P01 DA009467, DA-16187A, R01 DA016187] Funding Source: Medline
- NINDS NIH HHS [NS-39793, P50 NS039793-05, P50 NS039793] Funding Source: Medline
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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 2alpha-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.
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