Influence of Δ9-tetrahydrocannabinol on long-term neural correlates of threat extinction memory retention in humans
Influence of Δ9-tetrahydrocannabinol on long-term neural correlates of threat extinction memory retention in humans
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DOI：
10.1038/s41386-019-0416-6
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发表时间：
2019-09-01
影响因子：
7.6
通讯作者：
Rabinak, Christine A.
中科院分区：
文献类型：
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作者：
Hammoud, Mira Z.;Peters, Craig;Rabinak, Christine A.
Delta 9-tetrahydrocannabinol（THC）对人类威胁处理的影响的神经机制和持久性尚未完全了解。在此，我们使用功能性MRI和心理生理学工具来研究THC对条件性威胁消退学习机制的影响，以及THC在学习后1天和1周评估时对消退记忆保持的影响。健康参与者在第1天接受威胁条件反射。在第2天，参与者被随机分配在威胁消退学习前2小时服用一片THC或安慰剂（PBO）。在消退学习后1天和1周评估消退记忆保持。我们发现，四氢大麻酚管理增加杏仁核和腹内侧前额叶皮层（vmPFC）的激活在早期灭绝学习没有显着影响皮肤电导反应（SCR）。当学习后24小时测试消退记忆保留时，THC组对消退线索表现出较低的SCR，并且在消退网络内没有明显的消退诱导激活。当消光记忆保留测试1周后学习，THC组表现出显着降低的反应，在VMPFC和杏仁核内的熄灭线索，但显着增加VMPFC，海马，背侧前扣带皮层之间的功能耦合在此消光保留测试。我们的研究结果首次报告了一剂THC对威胁灭绝网络功能激活的长期影响，并揭示了参与一周后出现的功能连接的重大变化。我们强调需要进一步研究THC对威胁和焦虑回路的长期影响。
The neural mechanisms and durability of Delta 9-tetrahydrocannabinol (THC) impact on threat processing in humans are not fully understood. Herein, we used functional MRI and psychophysiological tools to examine the influence of THC on the mechanisms of conditioned threat extinction learning, and the effects of THC on extinction memory retention when assessed 1 day and 1 week from learning. Healthy participants underwent threat conditioning on day 1. On day 2, participants were randomized to take one pill of THC or placebo (PBO) 2-h before threat extinction learning. Extinction memory retention was assessed 1 day and 1 week after extinction learning. We found that THC administration increased amygdala and ventromedial prefrontal cortex (vmPFC) activation during early extinction learning with no significant impact on skin conductance responses (SCR). When extinction memory retention was tested 24 h after learning, the THC group exhibited lower SCRs to the extinguished cue with no significant extinction-induced activations within the extinction network. When extinction memory retention was tested 1 week after learning, the THC group exhibited significantly decreased responses to the extinguished cues within the vmPFC and amygdala, but significantly increased functional coupling between the vmPFC, hippocampus, and dorsal anterior cingulate cortex during this extinction retention test. Our results are the first to report a long-term impact of one dose of THC on the functional activation of the threat extinction network and unveil a significant change in functional connectivity emerging after a week from engagement. We highlight the need for further investigating the long-term impact of THC on threat and anxiety circuitry.