Lyons D, Friedman D P, Nader M A, Porrino L J
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, North Carolina 27157, USA.
J Neurosci. 1996 Feb 1;16(3):1230-8. doi: 10.1523/JNEUROSCI.16-03-01230.1996.
The functional consequences of acute cocaine administration in nonhuman primates were assessed using the quantitative 2-[14C]deoxyglucose method. Local rates of cerebral metabolism were determined after an intravenous infusion of 1.0 mg/kg cocaine or vehicle in six awake cynomolgus monkeys (Macaca fascicularis) trained to sit calmly in a primate chair. Cocaine administration decreased glucose utilization in a discrete set of structures that included both cortical and subcortical portions of the limbic system. Glucose metabolism in the core and shell of the nucleus accumbens was decreased markedly, and smaller decrements were observed in the caudate and anterior putamen. In addition, cocaine administration produced significant decreases in limbic cortex. Metabolism was decreased in orbitofrontal cortex (areas 11, 12o, 13, 13a, 13b), portions of the gyrus rectus including area 25, entorhinal cortex, and parts of the hippocampal formation. The cortical regions in which functional activity was altered provide dense projections to the nucleus accumbens, and the decreased activity in these projections may be responsible in part of the large alterations in functional activity within the ventral striatum. Decreased metabolism also was evident in the anterior nuclear group of the thalamus, raphe nuclei, and locus ceruleus. The acute cerebral metabolic effects of cocaine in the conscious macaque, therefore, were contained primarily within a set of interconnected limbic regions, including ventral prefrontal cortex, medial temporal regions, the ventral striatal complex, and anterior thalamus. The decreased rates of glucose metabolism reported here resemble decrements found using positron emission tomography in humans. In the rat, by contrast, metabolic activity increased and changes were focused in subcortical regions. The present results represent an important expansion of the neural circuitry on which cocaine acts in the monkey as compared with the rat, and this in turn implies that cocaine affects a broader spectra of behaviors in primates than in rodents.
采用定量2-[¹⁴C]脱氧葡萄糖法评估了急性给予可卡因对非人灵长类动物的功能影响。在6只经训练能安静地坐在灵长类动物椅上的清醒食蟹猴（猕猴）中，静脉注射1.0mg/kg可卡因或赋形剂后，测定局部脑代谢率。给予可卡因后，一组离散结构中的葡萄糖利用减少，这些结构包括边缘系统的皮质和皮质下部分。伏隔核核心和壳部的葡萄糖代谢显著降低，尾状核和前壳核也有较小程度的降低。此外，给予可卡因导致边缘皮质显著降低。眶额皮质（11区、12o区、13区、13a区、13b区）、包括25区在内的直回部分、内嗅皮质以及海马结构的部分区域代谢降低。功能活动发生改变的皮质区域向伏隔核提供密集投射，这些投射活动的降低可能部分导致腹侧纹状体内功能活动的大幅改变。丘脑前核群、中缝核和蓝斑核的代谢也明显降低。因此，可卡因对清醒猕猴的急性脑代谢作用主要局限于一组相互连接的边缘区域，包括腹侧前额叶皮质、颞叶内侧区域、腹侧纹状体复合体和丘脑前部。此处报道的葡萄糖代谢率降低类似于在人类中使用正电子发射断层扫描发现的降低情况。相比之下，在大鼠中，代谢活动增加且变化集中在皮质下区域。与大鼠相比，目前的结果表明可卡因在猴子中作用的神经回路有重要扩展，这反过来意味着可卡因对灵长类动物行为的影响范围比啮齿动物更广。
