Domino E F, Minoshima S, Guthrie S K, Ohl L, Ni L, Koeppe R A, Cross D J, Zubieta J
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-0632, USA.
Neuroscience. 2000;101(2):277-82. doi: 10.1016/s0306-4522(00)00357-2.
Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study. In each subject, positron emission tomographic images of regional cerebral metabolism of glucose with [18F]fluorodeoxyglucose were obtained in two conditions in the morning on different days: about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design. A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used. The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained. Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model. Peak plasma nicotine levels varied three-fold and the areas under the curve(0-30min) varied seven-fold among the individual subjects. Nicotine caused a small overall reduction in global cerebral metabolism of glucose but, when the data were normalized, several brain regions showed relative increases in activity. Cerebral structures specifically activated by nicotine (nicotine minus pepper, Z score >4.0) included: left inferior frontal gyrus, left posterior cingulate gyrus and right thalamus. The visual cortex, including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis, also showed an increase in regional cerebral metabolism of glucose with Z scores >3. 6. Structures with a decrease in regional cerebral metabolism of glucose (pepper minus nicotine) were the left insula and right inferior occipital gyrus, with Z scores >3.5. Especially important is the fact that the thalamus is activated by nicotine. This is consistent with the high density of nicotinic cholinoceptors in that brain region. However, not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors. The results are discussed in relation to the cognitive effects of nicotine.
11名不同种族的健康成年男性吸烟志愿者在夜间戒烟，参与了本研究。在不同日期的上午，对每位受试者在两种情况下进行了正电子发射断层扫描成像，以观察使用[18F]氟脱氧葡萄糖的局部脑葡萄糖代谢情况：分别在大约1-2毫克鼻腔尼古丁喷雾后约3分钟，以及在随机平衡设计中使用等量的辣椒辣椒油树脂活性安慰剂喷雾后。使用了一台能够进行15层水平脑切片扫描的西门子/CTI 931/08-12扫描仪。图像进一步转换为标准统一脑格式，从中获取了所有11名受试者的平均数据。使用逐像素t统计和光滑高斯模型在立体定向坐标中对图像进行分析。个体受试者的血浆尼古丁峰值水平变化了三倍，曲线下面积（0-30分钟）变化了七倍。尼古丁导致全脑葡萄糖代谢总体略有降低，但在数据归一化后，几个脑区的活动显示出相对增加。尼古丁特异性激活的脑结构（尼古丁减去辣椒，Z评分>4.0）包括：左侧额下回、左侧后扣带回和右侧丘脑。视觉皮层，包括左右楔叶和左侧枕颞外侧回梭状回，也显示局部脑葡萄糖代谢增加，Z评分>3.6。局部脑葡萄糖代谢降低的结构（辣椒减去尼古丁）是左侧脑岛和右侧枕下回，Z评分>3.5。特别重要的是，丘脑被尼古丁激活。这与该脑区烟碱型胆碱能受体的高密度一致。然而，并非所有受尼古丁影响的脑区都已知有许多烟碱型胆碱能受体。结合尼古丁的认知效应讨论了这些结果。
