Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans
Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans
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DOI：
10.1016/j.nlm.2013.09.009
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发表时间：
2014-09-01
影响因子：
2.7
通讯作者：
Phan, K. Luan
中科院分区：
文献类型：
--
作者：
Rabinak, Christine A.;Angstadt, Mike;Phan, K. Luan
在灭绝前给予Delta（9）-tetrahydrocannibinol（THC）有助于健康人回忆灭绝，来自动物研究的证据表明，这可能是通过增强腹内侧前额叶皮层（vmPFC）和海马（HIPP）内的大麻素系统而发生的，大脑结构对恐惧灭绝至关重要。然而，大麻素对人类灭绝记忆回忆的潜在神经回路的影响尚未得到证实。我们进行了一项功能性磁共振成像（fMRI）研究，采用随机、双盲、安慰剂对照、受试者间设计（N = 14/组），结合标准巴甫洛夫恐惧消退范式和健康成年志愿者口服屈大麻酚（合成THC）的急性药理学挑战。我们研究了四氢大麻酚对vmPFC和HIPP激活的影响时，测试回忆的消退学习后24小时的消退学习。与接受安慰剂的受试者相比，接受THC的受试者在消退记忆回忆期间对先前熄灭的条件刺激（CS + E）表现出增加的vmPFC和HIPP激活。这项研究提供了第一个证据表明，在人类恐惧消退期间，THC的预灭绝管理调节了前额叶边缘系统回路，并提示未来的研究，以测试大麻素激动剂是否可以挽救或纠正PTSD患者在消退回忆期间受损的行为和神经功能。最终，大麻素系统可能成为PTSD和其他恐惧学习相关疾病的创新干预策略（例如，药理学增强基于焦虑的治疗）的一个有前途的目标。(C)2013爱思唯尔公司All rights reserved.
Pre-extinction administration of Delta(9)-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely occurs via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N = 14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 h after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS + E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. (C) 2013 Elsevier Inc. All rights reserved.