Division of Psychiatry, Department of Brain Sciences, Imperial College London, United Kingdom.
Division of Psychiatry, Department of Brain Sciences, Imperial College London, United Kingdom.
Drug Alcohol Depend. 2021 Apr 1;221:108564. doi: 10.1016/j.drugalcdep.2021.108564. Epub 2021 Jan 29.
Opiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK) receptors have prominent effects on opiate reward and reinforcement, and human studies have found NK antagonism led to reductions in craving and withdrawal. However, its effect on brain mechanisms in opiate addiction has not yet been examined.
This study aims to assess the impact of NK antagonist aprepitant on heroin cue-elicited changes in blood-oxygenation level dependent (BOLD) signal in opiate dependent individuals undergoing detoxification. Participants will attend two scanning sessions and receive a single dose of aprepitant (320 mg) and a placebo in a randomised, cross-over design. During functional magnetic resonance imaging participants will undergo two runs of a cue reactivity task, which consists of passive viewing of drug cues or neutral cues in a block design fashion. We hypothesise that NK antagonism will attenuate the BOLD response to drug cues in the caudate nucleus and amygdala. Regions of interest were selected based on NK receptor density and their role in cue reactivity and craving.
阿片成瘾是一个重大的健康挑战，带来了巨大的社会代价。尽管减少伤害策略已经有效，但人们越来越需要新的治疗方法来进行戒毒和预防复发。临床前研究发现神经激肽 1（NK）受体对阿片类药物的奖赏和强化有显著影响，而人类研究发现 NK 拮抗剂可减少成瘾者的渴求感和戒断症状。然而，它对阿片成瘾的大脑机制的影响尚未被研究过。
本研究旨在评估 NK 拮抗剂 aprepitant 对接受戒毒治疗的阿片类药物依赖者在海洛因线索诱发的血氧水平依赖（BOLD）信号变化中的影响。参与者将参加两次扫描会议，并在随机、交叉设计中接受 aprepitant（320mg）和安慰剂的单次剂量。在功能磁共振成像期间，参与者将进行两次线索反应任务的运行，该任务由药物线索或中性线索的被动观看以块设计的方式组成。我们假设 NK 拮抗剂会减弱尾状核和杏仁核对药物线索的 BOLD 反应。感兴趣区域是根据 NK 受体密度及其在线索反应和渴求中的作用选择的。
