Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial.
Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial.
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DOI：
10.1038/mp.2016.39
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发表时间：
2017-01
影响因子：
11
通讯作者：
Foltin RW
中科院分区：
文献类型：
--
作者：
Dakwar E;Hart CL;Levin FR;Nunes EV;Foltin RW
反复吸毒可能会引发神经可塑性适应，从而减弱对自然奖励的敏感性，同时增加对渴望和药物线索的反应，从而发展为有问题的使用。使用一个已建立的实验室模型，旨在评估可卡因与金钱之间的显著性行为变化，我们评估了单次亚麻醉剂量的n-甲基-d -天冬氨酸受体拮抗剂氯胺酮对可卡因使用的影响，越来越多的证据表明，氯胺酮可能有助于纠正有问题的神经适应，并恢复非药物奖励的动机。我们发现，与对照组相比，氯胺酮在输注后超过24小时内显著减少可卡因自我给药，相对于基线减少67%，这是迄今为止在人类可卡因使用者中观察到的最明显的减少，也是第一个涉及兴奋剂或多巴胺激动剂作用以外的机制。这些发现标志着药物使用障碍药物开发的新方向。
Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, we evaluated the effect on cocaine use of a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine, which converging evidence suggests may work to correct problematic neuroadaptations and restore motivation for non-drug rewards. We found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 hours post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.