The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.
Division of Medical Psychology, Department of Psychiatry, University of Bonn, Bonn, Germany.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Aug;4(8):751-762. doi: 10.1016/j.bpsc.2019.04.006. Epub 2019 Apr 22.
Animal models of addiction suggest that the transition from incentive-driven drug use 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 neural cue reactivity in striatal circuits; however, these studies were not able to separate addiction-related from exposure-related adaptations.
To differentiate the adaptive changes, the current functional magnetic resonance imaging study examined behavioral and neural cue reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a nonusing reference group (n = 44).
Irrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striatal frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal striatal reactivity and decreased striatal limbic coupling during cue exposure. An exploratory analysis revealed that higher ventral caudate neural cue reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in nondependent users.
Taken together, the current findings suggest that exaggerated responses 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.
成瘾动物模型表明，从动机驱动的药物使用向习惯性、最终强迫性药物使用的转变是由腹侧纹状体线索控制向药物寻求的转变介导的。先前对人类大麻使用者的研究报告称，纹状体回路中的特质冲动性和神经线索反应性升高；然而，这些研究无法将与成瘾相关的适应与与暴露相关的适应区分开来。
为了区分适应性变化，当前的功能性磁共振成像研究检查了依赖（n=18）和非依赖（n=20）重度大麻使用者以及非使用者参考组（n=44）的行为和神经线索反应性。
无论依赖状态如何，大麻使用者都表现出较高的特质冲动性，以及对药物线索的腹侧纹状体反应性增加和纹状体额叶耦合增加。依赖使用者在线索暴露期间选择性地表现出背侧纹状体反应性和减少的纹状体边缘耦合。一项探索性分析表明，较高的腹侧尾状核神经线索反应性与依赖使用者更强的线索诱导唤醒和渴望相关，而在非依赖使用者中则相反。
综上所述，当前的研究结果表明，腹侧纹状体奖励系统的过度反应可能会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会促进向成瘾性使用的转变。
