Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Clinical Neuroscience Division, 67 President Street, MSC861, Charleston, SC 29425, United States.
Drug Alcohol Depend. 2013 Sep 1;132(1-2):195-201. doi: 10.1016/j.drugalcdep.2013.02.009. Epub 2013 Mar 14.
The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence.
Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training.
Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not.
Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples.
成瘾的发展以病理性的联想学习过程为标志,该过程使与药物使用相关的刺激具有激励显著性。最近,人们努力通过使用线索暴露疗法(辅以 D-环丝氨酸(DCS))来靶向该学习过程,DCS 被假设为增强消退学习的谷氨酸能药物。为了更好地了解 DCS 促进的消退对药物线索神经反应的影响,本研究报告了一项随机、双盲、安慰剂对照的 DCS 促进可卡因依赖线索暴露试验的 fMRI 结果。
25 名参与者完成了两次 MRI 扫描(干预前后),并进行了可卡因线索反应 fMRI 任务。干预包括 50mg DCS 或安慰剂,结合两次可卡因线索暴露和技能训练。
参与者在基线时表现出多种大脑区域的可卡因线索激活。从预研究扫描到后研究扫描,参与者在多个区域(例如伏隔核、尾状核、额极)经历了对线索的激活减少。出乎意料的是,安慰剂组参与者在左侧角回和颞中回以及外侧枕叶皮层的线索激活减少,而 DCS 组则没有。
三项针对可卡因依赖的 DCS 促进线索暴露治疗的试验发现,DCS 要么增加要么对可卡因线索的反应没有显著影响。本研究通过证明 DCS 可能预防可卡因线索在颞叶和枕叶脑区的消退,为该文献增添了新内容。尽管与过去的研究一致,但在更大的样本中得到复制之前,本研究的结果应被视为初步结果。