Department of Clinical, Neuro and Developmental Psychology, Vrije University Amsterdam, Amsterdam, The Netherlands.
Department of Psychiatry, University Medical Centre Groningen, Groningen, The Netherlands.
Eur Addict Res. 2024;30(3):163-180. doi: 10.1159/000538599. Epub 2024 May 6.
The development of cocaine use disorder in females is suggested to be more strongly related to neural mechanisms underlying stress-reactivity, whereas in males it is suggested to be more strongly related to neural mechanisms underlying drug cue-reactivity. Existing evidence, however, is based on neuroimaging studies that either lack a control group and/or have very small sample sizes that do not allow to investigate sex differences.
The main objective of the current study was to investigate sex differences in the neural correlates of cocaine and negative emotional cue-reactivity within high-risk intranasal cocaine users (CUs: 31 males and 26 females) and non-cocaine-using controls (non-CUs: 28 males and 26 females). A region of interest (ROI) analysis was applied to test for the main and interaction effects of group, sex, and stimulus type (cocaine cues vs. neutral cocaine cues and negative emotional cues vs. neutral emotional cues) on activity in the dorsal striatum, ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC).
There were no significant sex or group differences in cocaine cue-reactivity in any of the ROIs. Results did reveal significant emotional cue-reactivity in the amygdala and VS, but these effects were not moderated by group or sex. Exploratory analyses demonstrated that emotional cue-induced activation of the dACC and VS was negatively associated with years of regular cocaine use in female CUs, while this relationship was absent in male CUs.
While speculative, the sex-specific associations between years of regular use and emotional cue-reactivity in the dACC and VS suggest that, with longer years of use, female CUs become less sensitive to aversive stimuli, including the negative consequences of cocaine use, which could account for the observed "telescoping effect" in female CUs.
女性可卡因使用障碍的发展被认为与应激反应相关的神经机制更为密切，而男性则与药物线索反应相关的神经机制更为密切。然而，现有证据基于神经影像学研究，这些研究要么缺乏对照组，要么样本量非常小，无法调查性别差异。
本研究的主要目的是在高风险鼻内可卡因使用者（CUs：31 名男性和 26 名女性）和非可卡因使用者对照组（非-CUs：28 名男性和 26 名女性）中，调查可卡因和负性情绪线索反应的神经相关性的性别差异。采用感兴趣区（ROI）分析，以检验组、性别和刺激类型（可卡因线索与中性可卡因线索和负性情绪线索与中性情绪线索）对背侧纹状体、腹侧纹状体（VS）、杏仁核和背侧前扣带皮层（dACC）活性的主效应和交互效应。
在任何 ROI 中，可卡因线索反应均无显著的性别或组间差异。结果确实显示了杏仁核和 VS 中的显著情绪线索反应，但这些效应不受组或性别调节。探索性分析表明，情绪线索引起的 dACC 和 VS 的激活与女性 CUs 中常规可卡因使用的年限呈负相关，而在男性 CUs 中则不存在这种关系。
虽然这是推测性的，但 dACC 和 VS 中常规使用年限与情绪线索反应之间的性别特异性关联表明，随着使用年限的延长，女性 CUs 对厌恶刺激的敏感性降低，包括可卡因使用的负面后果，这可能解释了女性 CUs 中观察到的“望远镜效应”。
