From the Departments of Psychiatry and Radiology, Academic Medical Center, Amsterdam; the Spinoza Center for Neuroimaging, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam; and the Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Am J Psychiatry. 2016 Oct 1;173(10):1033-1042. doi: 10.1176/appi.ajp.2016.15040433. Epub 2016 Apr 15.
The authors investigated whether cocaine use disorder is associated with abnormalities in the neural underpinnings of aversive conditioning and extinction learning, as these processes may play an important role in the development and persistence of drug abuse.
Forty male regular cocaine users and 51 male control subjects underwent a fear conditioning and extinction protocol during functional MRI. Skin conductance response was measured throughout the experiment as an index of conditioned responses.
Cocaine users showed hyperresponsiveness of the amygdala and insula during fear conditioning, as well as hyporesponsiveness of the dorsomedial prefrontal cortex during extinction learning. In cocaine users, but not in control subjects, skin conductance responses were positively correlated with responsiveness of the insula, amygdala, and dorsomedial prefrontal cortex during fear conditioning but negatively correlated with responsiveness of the ventromedial prefrontal cortex during extinction learning.
Increased sensitivity to aversive conditioned cues in cocaine users might be a risk factor for stress-relief craving in cocaine use disorder. These results support the postulated role of altered aversive conditioning in cocaine use disorder and may be an important step in understanding the role of aversive learning in the pathology of cocaine use disorder.
作者研究了可卡因使用障碍是否与厌恶条件反射和消退学习的神经基础异常有关，因为这些过程可能在药物滥用的发展和持续中发挥重要作用。
40 名男性经常使用可卡因的患者和 51 名男性对照者在功能磁共振成像期间接受了恐惧条件反射和消退协议。在整个实验过程中测量皮肤电反应作为条件反应的指标。
可卡因使用者在恐惧条件反射时表现出杏仁核和岛叶的过度反应，以及在消退学习时背内侧前额叶皮层的反应性降低。在可卡因使用者中，但不在对照组中，皮肤电反应与恐惧条件反射时岛叶、杏仁核和背内侧前额叶皮层的反应性呈正相关，与消退学习时腹内侧前额叶皮层的反应性呈负相关。
可卡因使用者对厌恶条件刺激的敏感性增加可能是可卡因使用障碍中缓解压力的渴望的一个风险因素。这些结果支持了在可卡因使用障碍中改变的厌恶条件反射的假设作用，并可能是理解厌恶学习在可卡因使用障碍病理中的作用的重要一步。
