A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on craving in cocaine-dependent individuals
A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on craving in cocaine-dependent individuals
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DOI：
10.1007/s00213-011-2592-x
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Brady, Kathleen T.
中科院分区：
文献类型：
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作者：
Price, Kimber L.;Baker, Nathaniel L.;Brady, Kathleen T.
D-环丝氨酸（DCS）是一种谷氨酸N-甲基-D-天冬氨酸（NMDA）受体激动剂，可增强条件性恐惧反应的消退;初步数据表明，它可能有助于消除药物线索反应。本研究调查DCS对可卡因依赖受试者的可卡因线索渴求和药物使用的影响。32名受试者被随机分配到（1）仅接受DCS，（2）在疗程1和3之前接受DCS，安慰剂（PBO）在第2阶段之前，或（3）PBO仅在间隔1天进行的3个1小时可卡因线索暴露阶段中的每一个之前15分钟。在会议之前，期间和之后获得渴望评级。在最后一次提示会议后1周，对药物使用和提示诱导的渴望进行评估。重复呈现可卡因提示导致会议内和会议之间的渴望减少。DCS没有促进灭绝学习，可能会增强渴望。接受三次剂量DCS的组在第2次和第3次会议之前进行的基线评级中的渴望显著高于PBO组，并且在随访时具有显著更高的线索诱导的渴望。接受两剂DCS的组与PBO组没有差异。在消退后可卡因的使用没有组间差异，PBO组可卡因线索反应性的降低表明研究程序足以产生消退。在这些条件下，DCS并没有促进灭绝，并可能增强了渴望。进一步研究可卡因依赖的阿片类药物和消退应包括考虑可能对研究结果产生重大影响的程序变量。
d-Cycloserine (DCS), a partial glutamate N-methyl-d-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity.This study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects.Thirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session.Repeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use.The reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes.