Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task
Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task
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DOI：
10.1111/adb.12444
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发表时间：
2017-11-01
影响因子：
3.4
通讯作者：
Robbins, Trevor W.
中科院分区：
文献类型：
--
作者：
Nestor, Liam J.;Murphy, Anna;Robbins, Trevor W.
有一项协调一致的研究工作，旨在研究成瘾过程中潜在的大脑机制，这可能预示着治疗成瘾的新化合物的开发。一个目标是大脑的阿片系统，因为它在加强滥用物质的效果方面发挥了作用。物质依赖人群在额纹状体区域增加了预测药物复发的Mu阿片受体(MOR)的数量，并在处理非药物奖励的过程中显示出这些区域的干扰。纳曲酮目前被批准用于酒精和阿片类药物依赖，并可能通过阻断额叶纹状体奖赏回路中的MORS来补救这种干扰。因此，在一项随机、双盲、安慰剂对照的功能磁共振研究中，我们使用货币激励延迟(MID)任务，研究了纳曲酮对长期戒酒患者、酒精多物质依赖患者和对照组的非药物奖励的预期和工具性反应的潜在急性调节效应。我们报告，与酗酒者和对照组相比，酒精性多物质依赖组表现出更慢和更不准确的仪器反应，这在急性纳曲酮治疗后不那么明显。然而，纳曲酮治疗不能纠正额纹状体区域在奖赏期待时的干扰，并且在两个物质依赖组中都错过了奖赏。虽然我们还不能确定在酒精多物质依赖组中观察到的纳曲酮改善的潜在神经机制，但我们可以证实，这两个物质依赖组在中期任务中都表现出实质性的神经缺陷，尽管他们处于长期戒断状态。
There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled functional MRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and missed' rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.