Sex Differences in the Brain's Dopamine Signature of Cigarette Smoking
Sex Differences in the Brain's Dopamine Signature of Cigarette Smoking
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DOI：
10.1523/jneurosci.3661-14.2014
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发表时间：
2014-12-10
影响因子：
5.3
通讯作者：
Morris, Evan D.
中科院分区：
文献类型：
--
作者：
Cosgrove, Kelly P.;Wang, Shuo;Morris, Evan D.
吸烟是危害公众健康的主要因素。女性和男性吸烟的原因不同，戒烟治疗，如尼古丁贴片，优先对男性有益。这些性别差异的生物学基础尚不清楚。早期的PET研究报告了相互矛盾的发现，但都受到实验和/或分析限制的阻碍。我们的新图像分析技术lp-ntPET （Normandin et al., 2012; Morris et al., 2013; Kim et al., 2014）已经过优化，可捕获动态PET数据中短暂（仅持续几分钟）和高度局部化的多巴胺能事件。我们将分析技术与高分辨率脑部扫描和高频运动校正相结合，创建了捕获和表征吸烟对人类中脑边缘多巴胺系统影响的最佳实验。我们的主要发现是，男性吸烟者在PET扫描中吸烟时激活了右侧腹侧纹状体中的多巴胺，而女性吸烟者则没有。这一发现——男性比女性更能激活腹侧神经——与已有的观点一致，即男性吸烟是为了增强香烟的药物作用，而女性吸烟是出于其他原因，比如情绪调节和暗示反应。lp-ntPET分析产生了一个新的多维端点：个体受试者的神经递质释放体素水平的时间模式（“DA电影”）。通过定量检查这些终点，我们证明了吸烟的多巴胺能反应的时间在男性和女性之间是不同的。男性在腹侧纹状体反应一致且迅速，而女性在背壳核的一个离散亚区反应更快。
Cigarette smoking is a major public health danger. Women and men smoke for different reasons and cessation treatments, such as the nicotine patch, are preferentially beneficial to men. The biological substrates of these sex differences are unknown. Earlier PET studies reported conflicting findings but were each hampered by experimental and/or analytical limitations. Our new image analysis technique, lp-ntPET (Normandin et al., 2012; Morris et al., 2013; Kim et al., 2014), has been optimized for capturing brief (lasting only minutes) and highly localized dopaminergic events in dynamic PET data. We coupled our analysis technique with high-resolution brain scanning and high-frequency motion correction to create the optimal experiment for capturing and characterizing the effects of smoking on the mesolimbic dopamine system in humans. Our main finding is that male smokers smoking in the PET scanner activate dopamine in the right ventral striatum during smoking but female smokers do not. This finding-men activating more ventrally than women-is consistent with the established notion that men smoke for the reinforcing drug effect of cigarettes whereas women smoke for other reasons, such as mood regulation and cue reactivity. lp-ntPET analysis produces a novel multidimensional endpoint: voxel-level temporal patterns of neurotransmitter release ("DA movies") in individual subjects. By examining these endpoints quantitatively, we demonstrate that the timing of dopaminergic responses to cigarette smoking differs between men and women. Men respond consistently and rapidly in the ventral striatum whereas women respond faster in a discrete subregion of the dorsal putamen.