The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
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DOI：
10.1016/j.drugalcdep.2015.09.021
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发表时间：
2015-11-01
影响因子：
4.2
通讯作者：
Gray KM
中科院分区：
文献类型：
--
作者：
Froeliger B;McConnell PA;Stankeviciute N;McClure EA;Kalivas PW;Gray KM
长期暴露于滥用药物会破坏额纹状体谷氨酸传输，这反过来又会导致药物寻求。在动物模型中，N-乙酰半胱氨酸使失调的额纹状体多巴胺能神经传递正常化，并防止恢复药物寻求;然而，N-乙酰半胱氨酸对人类额纹状体电路功能和维持戒烟的影响尚不清楚。因此，目前的研究测试了N-乙酰半胱氨酸与更强的额纹状体静息状态功能连接（rsFC）相关的假设，减弱了尼古丁戒断，并有助于吸烟者在研究期间保持戒烟。本研究探讨了N-乙酰半胱氨酸对额纹状体rsFC、尼古丁戒断症状和维持戒断的影响。健康成人、非寻求治疗的吸烟者（N=16;平均（SD）年龄36.5±11.9;烟/天15.8±6.1;年/吸烟15.7±8.9）被随机分配至2400 mg N-乙酰半胱氨酸（1200 mg b.i.d.）或安慰剂在3天半的金钱激励戒烟过程中。在每个戒烟日，以数字方式收集情绪和渴望的测量值，参与者参加实验室访问以评估吸烟（即，空气中的一氧化碳[CO]）。在第4天，参与者接受了fMRI扫描。与安慰剂（n=8）相比，N-乙酰半胱氨酸组（n=8）中的吸烟者保持禁欲，报告较少的渴望和较高的积极情感（所有p <.01），并且伴随地在腹侧纹状体节点、内侧前额叶皮质和楔前叶-关键默认模式网络节点以及小脑之间表现出更强的rsFC [p<.025; FWE]）。总之，这些研究结果表明，N-乙酰半胱氨酸可能会积极影响潜在的失调皮质纹状体连接，有助于重建奖励处理，并有助于保持戒烟尝试后立即禁欲。
Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; yrs/smoking 15.7±8.9) were randomized to a double-blind course of 2400 mg N-Acetylcysteine (1200 mg b.i.d.) or placebo over the course of 3 ½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected digitally and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p’s <.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus—key default mode network nodes, and the cerebellum [p<.025; FWE]). Taken together, these findings suggest that N-Acetylcysteine may positively affect potentially dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.