Smoking produces rapid rise of [11C]nicotine in human brain
Smoking produces rapid rise of [11C]nicotine in human brain
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DOI：
10.1007/s00213-010-1809-8
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Boswell, Mark V.
中科院分区：
文献类型：
--
作者：
Berridge, Marc S.;Apana, Scott M.;Boswell, Mark V.
药物到达大脑的速度的变化会影响许多不同的药物作用，也被认为会影响成瘾的倾向。例如，可卡因和尼古丁的快速静脉注射在产生快感效应、耐受性、精神敏化和诱导基因表达方面更有效。吸烟被认为会导致大脑中尼古丁的快速上升，但这是否属实从未得到充分的解决。因此，在这项研究中，我们试图确定吸烟尼古丁在人脑中的真实上升率，并将其与以前的静脉注射尼古丁进行比较。在人类受试者单次吸含[C-11]尼古丁的香烟后，获得了肺和脑区域的正电子发射断层扫描以及动脉和静脉血液曲线。单次吸后尼古丁浓度的上升很快，在大多数受试者中，在药团到达脑中的15秒内达到最大脑水平的50%以上。这一上升速度比以前使用静脉注射的研究中观察到的要快得多。单次吸入在人脑中的吸收速度足够快，因此快速上升速度有助于吸烟者对尼古丁的依赖是合理的。
Variation in the rate at which drugs reach the brain influences many different drug effects and is also thought to influence liability to addiction. For example, rapid intravenous delivery of cocaine and nicotine is more effective in producing hedonic effects, tolerance, psychomotor sensitization, and in inducing gene expression. Smoking is thought to result in an especially rapid rate of rise of nicotine in the brain, but whether this is true has never been adequately addressed. Thus, in this study, we sought to determine the true rate of rise of smoked nicotine in human brain and compare this with previous intravenous nicotine delivery.Positron emission tomography scans of lung and brain regions and arterial and venous blood curves were obtained in human subjects after single puffs from cigarettes formulated with [C-11]nicotine.The rise of nicotine concentration following a single puff was rapid, reaching more than 50% of maximum brain levels within 15 s of bolus arrival in the brain in most subjects. This rate of rise was considerably faster than that seen in previous studies using intravenous administration.Uptake in human brain from a single inhalation was sufficiently rapid that it is plausible that fast rate-of-rise contributes to nicotine dependence in smokers.