Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21228, USA.
Biol Psychiatry. 2013 Feb 1;73(3):280-8. doi: 10.1016/j.biopsych.2012.06.034. Epub 2012 Aug 29.
Dopaminergic activity plays a role in mediating the rewarding aspects of abused drugs, including nicotine. Nicotine modulates the reinforcing properties of other motivational stimuli, yet the mechanisms of this interaction are poorly understood. This study aimed to ascertain the impact of nicotine exposure on neuronal activity associated with reinforcing outcomes in dependent smokers.
Smokers (n = 28) and control subjects (n = 28) underwent functional imaging during performance of a monetary incentive delay task. Using a randomized, counterbalanced design, smokers completed scanning after placement of a nicotine or placebo patch; nonsmokers were scanned twice without nicotine manipulation. In regions along dopaminergic pathway trajectories, we considered event-related activity for valence (reward/gain vs. punishment/loss), magnitude (small, medium, large), and outcome (successful vs. unsuccessful).
Both nicotine and placebo patch conditions were associated with reduced activity in regions supporting anticipatory valence, including ventral striatum. In contrast, relative to controls, acute nicotine increased activity in dorsal striatum for anticipated magnitude. Across conditions, anticipatory valence-related activity in the striatum was negatively associated with plasma nicotine concentration, whereas the number of cigarettes daily correlated negatively with loss anticipation activity in the medial prefrontal cortex only during abstinence.
These data suggest a partial dissociation in the state- and trait-specific effects of smoking and nicotine exposure on magnitude- and valence-dependent anticipatory activity within discrete reward processing brain regions. Such variability may help explain, in part, nicotine's impact on the reinforcing properties of nondrug stimuli and speak to the continued motivation to smoke and cessation difficulty.
多巴胺活动在介导包括尼古丁在内的滥用药物的奖赏方面发挥作用。尼古丁调节其他动机刺激的强化特性,但这种相互作用的机制知之甚少。本研究旨在确定尼古丁暴露对依赖吸烟者与强化结果相关的神经元活动的影响。
吸烟者(n=28)和对照受试者(n=28)在执行货币奖励延迟任务期间接受功能成像。使用随机、平衡设计,吸烟者在放置尼古丁或安慰剂贴片后完成扫描;非吸烟者在没有尼古丁处理的情况下进行了两次扫描。在多巴胺能途径轨迹的区域中,我们考虑了与效价(奖励/增益与惩罚/损失)、幅度(小、中、大)和结果(成功与失败)相关的事件相关活动。
尼古丁和安慰剂贴片条件都与支持预期效价的区域(包括腹侧纹状体)的活动减少有关。相比之下,与对照组相比,急性尼古丁增加了预期幅度时背侧纹状体的活动。在所有条件下,纹状体中与预期效价相关的活动与血浆尼古丁浓度呈负相关,而在禁欲期间,每日吸烟量与内侧前额叶皮质的损失预期活动呈负相关。
这些数据表明,吸烟和尼古丁暴露对离散奖励处理脑区中与幅度和效价相关的预期活动的状态和特质特异性影响存在部分分离。这种可变性可能部分解释了尼古丁对非药物刺激的强化特性的影响,并说明了持续的吸烟动机和戒烟困难。