Mapping dopamine function in primates using pharmacologic magnetic resonance imaging
Mapping dopamine function in primates using pharmacologic magnetic resonance imaging
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DOI：
10.1523/jneurosci.1558-04.2004
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发表时间：
2004-10-27
影响因子：
5.3
通讯作者：
Isacson, O
中科院分区：
文献类型：
--
作者：
Jenkins, BG;Sanchez-Pernaute, R;Isacson, O
多巴胺（DA）受体在帕金森病、精神分裂症和药物滥用等多种病理中起着重要作用。我们使用安非他明的挑战结合药理学磁共振成像（phMRI）映射DA相关的电路在非人灵长类动物具有高灵敏度和空间分辨率。使用正电子发射断层扫描（PET）和phMRI纵向研究了7只对照食蟹猴和10只MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）治疗的帕金森病灵长类动物。安非他明激发（2.5 mg/kg，i. v.）在对照组猴子中，在许多先前未描述的脑区域，如束旁丘脑、中央前回和小脑齿状核，相对脑血容量（rCBV）增加。在高空间分辨率的情况下，我们还能够容易地识别前扣带回、黑质、腹侧被盖区、尾状核（尾和头）、壳核和丘脑核中的rCBV变化。安非他明引起枕叶和后顶叶皮质rCBV降低。帕金森病灵长类动物对安非他明的反应明显减弱，丘脑束旁核和丘脑束旁核相对较少。黑质rCBV损失与多巴胺转运蛋白PET成像和行为测量之间存在显著相关性。通过2 α-甲氧甲酯-3 β-（4-氟苯基）托烷与多巴胺转运蛋白结合来定义部分病变的猴子在安非他明刺激后显示出运动前区和运动皮质的募集，类似于帕金森病患者在运动任务中观察到的情况。这些数据表明，phMRI是一个强大的工具，用于评估与正常和功能障碍的DA在灵长类动物脑回路的动态变化。
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.