Cigarette smoking saturates brain α4β2 nicotinic acetylcholine receptors
Cigarette smoking saturates brain α4β2 nicotinic acetylcholine receptors
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DOI：
10.1001/archpsyc.63.8.907
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发表时间：
2006-08-01
影响因子：
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通讯作者：
Mukhin, Alexey G.
中科院分区：
文献类型：
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作者：
Brody, Arthur L.;Mandelkern, Mark A.;Mukhin, Alexey G.
内容：2-[F-18]氟-3-（2（S）-氮杂环丁烷甲氧基）吡啶（2-F-A-85380，缩写为2-FA）是最近开发的一种放射性配体，可通过正电子发射断层扫描（PET）显像人脑α（4）β（2）* 烟碱乙酰胆碱受体（nAChRs）。目的：为了确定吸烟对烟草依赖吸烟者α 4 β 2 nAChR占有率的影响，设计：进行了14次2-FA PET扫描。在PET扫描期间，受试者吸烟5种量中的1种（无、1吸、3吸、1整支烟或至饱[2（2）/（1）至3支烟]）。地点：学术脑成像中心。参与者：11名烟草依赖吸烟者主要结果测量：吸烟对α（4）β（2）* nAChR占用率的剂量依赖性影响，如在nAChR丰富的脑区域中使用2-FA和PET测量的。吸烟0.13（1至2喷）支香烟导致吸烟后3.1小时内α（4）β（2）* nAChR占据50%。吸一整支烟（或更多）导致超过88%的受体占用率，并伴随着对香烟的渴望减少。静脉血浆尼古丁浓度为0.87 ng/mL（大约是典型的每日吸烟者达到的水平的（25）/（1））与α（4）β（2）* nAChRs的50%占用相关。典型的日常吸烟者吸烟量导致几乎完全占据α（4）β（2）* nAChR，表明烟草依赖性吸烟者全天保持α（4）β（2）* nAChR饱和。由于尼古丁与α（4）β（2）* nAChR的长期结合与这些受体的脱敏有关，因此本文发现的受体占据程度表明，吸烟可能通过维持nAChR处于脱敏状态而导致戒断缓解。
Context: 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380, abbreviated as 2-FA) is a recently developed radioligand that allows for visualization of brain alpha(4)beta(2)* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans.Objective: To determine the effect of cigarette smoking on alpha(4)beta(2)* nAChR occupancy in tobacco-dependent smokers.Design: Fourteen 2- FA PET scanning sessions were performed. During the PET scanning sessions, subjects smoked 1 of 5 amounts (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2(2)/(1) to 3 cigarettes]).Setting: Academic brain imaging center.Participants: Eleven tobacco-dependent smokers (paid volunteers).Main Outcome Measure: Dose-dependent effect of smoking on occupancy of alpha(4)beta(2)* nAChRs, as measured with 2-FA and PET in nAChR-rich brain regions.Results: Smoking 0.13 (1 to 2 puffs) of a cigarette resulted in 50% occupancy of alpha(4)beta(2)* nAChRs for 3.1 hours after smoking. Smoking a full cigarette (or more) resulted in more than 88% receptor occupancy and was accompanied by a reduction in cigarette craving. A venous plasma nicotine concentration of 0.87 ng/mL (roughly (25)/(1)th of the level achieved in typical daily smokers) was associated with 50% occupancy of alpha(4)beta(2)* nAChRs.Conclusions: Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of alpha(4)beta(2)* nAChRs, indicating that tobacco-dependent smokers maintain alpha(4)beta(2)* nAChR saturation throughout the day. Because prolonged binding of nicotine to alpha(4)beta(2)* nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state.