Sussex Addiction Research and Intervention Centre (SARIC), School of Psychology, University of Sussex, Brighton, BN1 9QH, United Kingdom,
Sussex Neuroscience, University of Sussex, Brighton, BN1 9QH, United Kingdom.
J Neurosci. 2018 May 30;38(22):5182-5195. doi: 10.1523/JNEUROSCI.0019-18.2018. Epub 2018 May 14.
Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home ( < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home ( < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes. The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.
先前的研究表明，海洛因和可卡因成瘾者更喜欢在不同的环境中使用这些药物：海洛因主要在家中，可卡因主要在户外。在这里，我们研究了环境是否会以类似的方式调节对这些药物的情感和神经反应。首先，我们使用一种新的情感任务，根据男性和女性吸毒者的回忆，来评估在不同环境中使用海洛因或可卡因所产生的情感状态。然后，我们使用 fMRI 监测男性吸毒者在药物意象（再现用药环境）期间的神经活动。与我们的工作假设一致，大多数参与者报告说，海洛因的情感效价从家中主要愉悦转变为户外主要不愉快（<0.0001）。可卡因则相反，即大多数参与者发现可卡因在户外使用时愉快，而在家中使用时不愉快（<0.0014）。此外，我们发现了一种双重分离，作为药物和环境意象的功能，在左侧 PFC 和尾状核以及小脑双侧的 BOLD 信号变化（所有 值<0.01），这表明额纹状体小脑网络参与了药物诱导情感的情境化。总之，我们报告说，同一环境可以以相反的方向影响人类对精神兴奋剂和阿片类药物的情感和神经反应，这增加了这两种药物类别的奖励效应具有不同基础的证据。成瘾药物的奖励效应通常被认为依赖于共同的基础。然而，环境影响可以揭示精神兴奋剂和阿片类药物之间的显著差异。在这里，我们使用情感任务和 fMRI 来探索环境对海洛因与可卡因在成瘾个体中的反应的影响。仅仅从一个环境转移到另一个环境，就会显著降低海洛因的快感，但会增加可卡因的快感，反之亦然。在额纹状体小脑网络的活动中也观察到类似的双重分离。这些发现表明，阿片类药物和精神兴奋剂的作用取决于可分离的心理和神经基础，而成瘾的治疗方法应该考虑到不同药物类别的特殊性和用药环境。
