Cue-reactivity in the ventral striatum characterizes heavy cannabis use, whereas reactivity in the dorsal striatum mediates dependent use
Cue-reactivity in the ventral striatum characterizes heavy cannabis use, whereas reactivity in the dorsal striatum mediates dependent use
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DOI：
10.1101/516385
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发表时间：
2019-01
期刊：
影响因子：
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通讯作者：
Xinqi Zhou;Kaeli Zimmermann;F. Xin;Weihua Zhao;Roelinka T Derckx;Anja Sassmannshausen;D. Scheele;R. Hurlemann;B. Weber;K. Kendrick;B. Becker
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文献类型：
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作者：
Xinqi Zhou;Kaeli Zimmermann;F. Xin;Weihua Zhao;Roelinka T Derckx;Anja Sassmannshausen;D. Scheele;R. Hurlemann;B. Weber;K. Kendrick;B. Becker
成瘾的动物模型表明，从激励驱动到习惯性并最终强迫性药物使用的转变是由对药物寻求的腹侧纹状体向背侧纹状体的线索控制转变所介导的。先前对人类大麻使用者的研究报告了纹状体回路中特征冲动性和线索反应性的升高，然而，这些研究无法将成瘾相关的适应与暴露相关的适应区分开来。方法为了区分适应性变化，本研究通过功能磁共振成像检测了依赖（n = 18）和非依赖（n = 20）重度大麻使用者以及未使用参照组（n = 44）的行为和神经线索反应性。结果无论大麻依赖状态如何，大麻使用者在药物提示下表现出更高的特质冲动，以及腹侧纹状体反应性和纹状体-额叶耦合性的增加。依赖使用者选择性地表现出背纹状体反应性和纹状体-边缘耦合降低。一项探索性分析显示，依赖者腹侧尾状核的高线索反应性与更强的线索诱导唤醒和渴望相关，而非依赖者则相反。综上所述，目前的研究结果表明，腹侧纹状体奖励系统的激励敏化可能促进人类过度使用药物，而参与习惯形成的背侧纹状体系统的适应可能促进向成瘾使用的过渡。
Background Animal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations. Methods To differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and non-dependent (n = 20) heavy cannabis users and a non-using reference group (n = 44). Results Irrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users. Conclusions Together the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.