Effects of varenicline on smoking cue–triggered neural and craving responses.
Effects of varenicline on smoking cue–triggered neural and craving responses.
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DOI：
10.1001/archgenpsychiatry.2010.190
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发表时间：
2011-05
影响因子：
--
通讯作者：
Childress, Anna Rose
中科院分区：
文献类型：
--
作者：
Franklin, Teresa;Wang, Ze;Suh, Jesse J.;Hazan, Rebecca;Cruz, Jeffrey;Li, Yin;Goldman, Marina;Detre, John A.;O'Brien, Charles P.;Childress, Anna Rose
伐尼克兰是一种有效的戒烟药物，作为α4β2烟碱乙酰胆碱受体部分激动剂发挥作用。它通过减少戒烟期间的戒断症状和减少吸烟时尼古丁的强化作用间接影响多巴胺能奖励系统。我们推测伐尼克兰可能有第三种机制来减弱奖励相关的腹侧纹状体和内侧眶额皮质对吸烟线索的反应，并与吸烟线索引起的渴望减少有关。一个实验室模型的条件反射和动脉自旋标记灌注功能磁共振成像，一个生物标志物的区域大脑活动，被用来测试我们的假设。灌注功能磁共振成像是定量的，在整个时间内是稳定的，有利于测量药物诱导的神经修饰在大脑中响应于挑战（吸烟提示暴露）和大脑在静息状态（无激发）。吸烟者在休息期间和吸烟提示暴露期间进行了成像，之前和之后进行了为期3周的随机安慰剂对照药物治疗方案。受试者非禁欲明确检查伐尼克兰对线索反应独立的撤退的影响。费城宾夕法尼亚大学成瘾研究中心。受试者是尼古丁依赖的吸烟者，他们对当地电台和Listservs上的广告做出反应，参加了一项药物相关的研究，该研究明确指出“这不是一项戒烟研究”和“吸烟者可能正在考虑但目前不考虑戒烟”。随机分组前吸烟线索与不吸烟线索激活腹侧纹状体和内侧眶额皮质（t=3.77），并引起主观报告的渴望（P= 0.006）。渴求报告与后扣带回活动增加相关（t=4.11）。服用伐尼克兰可以减少吸烟提示引起的腹侧纹状体和内侧眶额皮质反应（t值为-3.75至-5.63），并减少自我报告的吸烟提示引起的渴望，而安慰剂治疗的受试者表现出与随机化前观察到的反应相似的反应。伐尼克兰诱导的静息状态下大脑外侧眶额皮层的激活（t=5.63）预示着内侧眶额皮层的吸烟提示反应钝化（r=-0.74）。伐尼克兰在奖励激活的内侧眶额皮质和奖励评估外侧眶额皮质中的相互作用是减少吸烟提示反应的基础，揭示了一种独特的新作用，可能有助于其临床疗效。
Varenicline, an effective smoking cessation medication, functions as an α4β2 nicotinic acetylcholine receptor partial agonist. It indirectly affects the dopaminergic reward system by reducing withdrawal symptoms during abstinence and by decreasing the reinforcement received from nicotine while smoking. We hypothesize that varenicline would have a third mechanism to blunt responses to smoking cues in the reward-related ventral striatum and medial orbitofrontal cortex and would be associated with a reduction in smoking cue–elicited craving. A laboratory model of conditioned responding and arterial spin-labeled perfusion functional magnetic resonance imaging, a biomarker of regional brain activity, was used to test our hypothesis. Perfusion functional magnetic resonance imaging is quantitative and stable across time, facilitating the measurement of medication-induced neural modifications in the brain in response to a challenge (smoking cue exposure) and in the brain in the resting condition (without provocation). Smokers were imaged during rest and during smoking cue exposure before and after a 3-week randomized placebo-controlled medication regimen. Subjects were nonabstinent to explicitly examine the effects of varenicline on cue reactivity independent of withdrawal. Center for the Study of Addictions, University of Pennsylvania, Philadelphia. Subjects were nicotine-dependent smokers who responded to advertisements placed on local radio and Listservs to participate in a medication-related research study that specifically stated “this is not a Quit Smoking Study” and “smokers may be contemplating but not currently considering quitting.” Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t=3.77) and elicited subjective reports of craving (P=.006). Craving reports correlated with increased activity in the posterior cingulate (t=4.11). Administration of varenicline diminished smoking cue– elicited ventral striatum and medial orbitofrontal cortex responses (t values from −3.75 to −5.63) and reduced self-reported smoking cue–elicited craving, whereas placebo-treated subjects exhibited responses similar to those observed prior to randomization. Varenicline-induced activation of lateral orbitofrontal cortex in the brain at rest (t=5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r=−0.74). Varenicline’s reciprocal actions in the reward-activated medial orbitofrontal cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a diminished smoking cue response, revealing a distinctive new action that likely contributes to its clinical efficacy.
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DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
7.6
作者：
Franklin, TR;Druhan, JP
通讯作者：
Druhan, JP
影响因子：
7.6
作者：
Franklin, Teresa R.;wang, Ze;Childress, Anna Rose
通讯作者：
Childress, Anna Rose
影响因子：
6
作者：
Drummond, DC
通讯作者：
Drummond, DC
影响因子：
5.7
作者：
Hariri, AR;Tessitore, A;Weinberger, DR
通讯作者：
Weinberger, DR