Ghasemian Sadegh, Vardanjani Marzieh M, Sheibani Vahid, Mansouri Farshad A
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Cognitive Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
J Psychopharmacol. 2022 Oct;36(10):1151-1160. doi: 10.1177/02698811221112952. Epub 2022 Aug 16.
Deficits in cognitive control, particularly inhibition ability, play crucial roles in susceptibility, progress, and relapse to opioid addiction. However, it is unclear when and how such deficits develop and interact with repeated exposures to prescribed opioids.
Using macaque monkey (), as an animal model with high translational merits in cognitive neuroscience, we tried to delineate alterations of inhibition ability in the course of repeated exposures to morphine.
Monkeys were trained to perform stop-signal task and then we closely monitored their inhibition ability before exposure, after initial exposure, and following repeated exposures to morphine when they experienced abstinent periods. We also assessed morphine-induced conditioned place preference (CPP) in these monkeys to monitor the long-lasting effects of morphine on other behaviors.
Compared to the baseline level, monkeys' inhibition ability was significantly enhanced after initial exposure to morphine (early phase); however, it became significantly attenuated after repeated exposures (late phase). These alterations occurred while monkeys consistently expressed the morphine-induced CPP over the course of morphine exposure.
Our findings indicate that repeated and scheduled exposures to morphine, which is akin to its clinical and recreational use, lead to dynamic alterations in primates' cognitive control depending on the extent of exposure. Enhancement of inhibition after limited exposure might provide opportunities to intervene and prevent the progress and culmination of opioid addiction, which is characterized by disinhibited drug-seeking and consumption.
认知控制缺陷，尤其是抑制能力，在阿片类药物成瘾的易感性、进展和复发中起关键作用。然而，目前尚不清楚这些缺陷何时以及如何发展，以及与反复接触处方阿片类药物之间如何相互作用。
使用猕猴作为认知神经科学中具有高度转化价值的动物模型，我们试图描绘在反复接触吗啡过程中抑制能力的变化。
训练猴子执行停止信号任务，然后在接触前、初次接触后以及在经历戒断期时反复接触吗啡后，密切监测它们的抑制能力。我们还评估了这些猴子中吗啡诱导的条件性位置偏好（CPP），以监测吗啡对其他行为的长期影响。
与基线水平相比，猴子在初次接触吗啡后（早期阶段）抑制能力显著增强；然而，在反复接触后（后期阶段），抑制能力显著减弱。这些变化发生在猴子在吗啡接触过程中持续表现出吗啡诱导的CPP的同时。
我们的研究结果表明，反复且按计划接触吗啡，类似于其临床和娱乐用途，会根据接触程度导致灵长类动物认知控制的动态变化。有限接触后抑制能力的增强可能为干预和预防以不受抑制的药物寻求和消费为特征的阿片类药物成瘾的进展和最终形成提供机会。
