fMRI of cocaine self-administration in macaques reveals functional inhibition of basal ganglia.
fMRI of cocaine self-administration in macaques reveals functional inhibition of basal ganglia.
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DOI：
10.1038/npp.2011.1
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发表时间：
2011-05
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影响因子：
--
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可卡因诱导的神经化学和代谢反应之间的差异，人类和啮齿类动物的动机使用非人灵长类动物（NHP）的模型在人类受试者中重复接触可卡因的后果。为了表征NHP脑中可卡因输注的功能反应，我们采用对比增强的功能磁共振成像在非特遣队注射药物和自我管理的可卡因在磁铁。皮质醇显著降低基底神经节和运动/前运动皮层的脑血容量（CBV），并对前额叶皮层产生轻微的功能抑制。没有脑区表现出显着的CBV升高可卡因的挑战。NHP脑中的这些效应与可卡因诱导的大鼠fMRI反应的信号相反，但与先前基于葡萄糖代谢的NHP测量结果一致。由于纹状体的D2到D1受体的比例在人类和NHP比大鼠大，我们假设D2受体结合的抑制作用主导灵长类动物的功能反应，而兴奋性D1受体刺激主导大鼠。如果NHP准确地模拟了人类对可卡因的反应，那么在人类可卡因滥用人群中D2受体的下调可以预期会减弱可卡因诱导的功能反应，从而导致可卡因输注后人类基底神经节中报告的微弱和可变的fMRI反应。
Disparities in cocaine-induced neurochemical and metabolic responses between humans and rodents motivate the use of non-human primates (NHP) to model consequences of repeated cocaine exposure in human subjects. In order to characterize the functional response to cocaine infusion in NHP brain, we employed contrast-enhanced fMRI during both non-contingent injection of drug and self-administration of cocaine in the magnet. Cocaine robustly decreased cerebral blood volume (CBV) throughout basal ganglia and motor/pre-motor cortex and produced subtle functional inhibition of prefrontal cortex. No brain regions exhibited significant elevation of CBV in response to cocaine challenge. Theses effects in NHP brain are opposite in sign to the cocaine-induced fMRI response in rats but consistent with prior measurements in NHP based upon glucose metabolism. Because the striatal ratio of D2 to D1 receptors is larger in humans and NHP than rats, we hypothesize that the inhibitory effects of D2-receptor binding dominates the functional response in primates, whereas excitatory D1-receptor stimulation predominates in the rat. If the NHP accurately models the human response to cocaine, down-regulation of D2 receptors in human cocaine-abusing populations can be expected to blunt cocaine-induced functional responses, contributing to the weak and variable fMRI responses reported in human basal ganglia following cocaine infusion.
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影响因子：
5.3
作者：
Bradberry, CW
通讯作者：
Bradberry, CW
影响因子：
3.3
作者：
CHARNAY, Y;LEGER, L;BOURAS, C
通讯作者：
BOURAS, C
慢性可卡因自我给药的禁欲改变了恒河猴中的纹状体多巴胺系统。
DOI：
10.1038/npp.2008.135
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
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影响因子：
3.3
作者：
Griswold, MA;Jakob, PM;Haase, A
通讯作者：
Haase, A
影响因子：
7.6
作者：
HALL, H;SEDVALL, G;FARDE, L
通讯作者：
FARDE, L