Effect of the Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 2 AZD8529 on Incubation of Methamphetamine Craving After Prolonged Voluntary Abstinence in a Rat Model.
Effect of the Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 2 AZD8529 on Incubation of Methamphetamine Craving After Prolonged Voluntary Abstinence in a Rat Model.
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DOI：
10.1016/j.biopsych.2015.02.018
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发表时间：
2015-10-01
影响因子：
10.6
通讯作者：
Shaham Y
中科院分区：
文献类型：
--
作者：
Caprioli D;Venniro M;Zeric T;Li X;Adhikary S;Madangopal R;Marchant NJ;Lucantonio F;Schoenbaum G;Bossert JM;Shaham Y
线索诱导的甲基苯丙胺渴求在长时间强迫（实验者强加的）戒断毒品（甲基苯丙胺渴求的潜伏期）后增加。在这里，我们确定这种孵化现象是否会在促进自愿（自我强加）禁欲的条件下发生。我们还确定了新型mGluR2阳性变构调节剂AZD8529在强迫或自愿戒断后对甲基苯丙胺渴望的影响。我们训练大鼠自我喂食美味食物（6次），然后在两种条件下自我喂食甲基苯丙胺：12次（每天9小时）或50次（每天3小时）。然后，我们在1天或21天的戒断后评估线索诱导的甲基苯丙胺寻求灭绝试验。在两次测试之间，大鼠要么被迫禁欲（不接触与食物或药物配对的杠杆），要么自愿禁欲19天（通过甲基苯丙胺和美味食物之间的离散选择程序实现；每天20次试验）。我们还确定了皮下注射AZD8529（20和40 mg/kg）对线索诱导的甲基苯丙胺在强迫或自愿戒断后1天或21天的影响。在训练条件和戒断条件下，戒断21天后线索诱导的消失实验中寻找甲基苯丙胺的比例高于戒断1天后（甲基苯丙胺渴望潜伏期）。AZD8529在第21天减少线索诱导的甲基苯丙胺寻求，但在第1天没有强迫或自愿戒断。我们引入了一种新的动物模型来研究长期自愿戒断后药物渴望和线索诱导的药物寻求的潜伏期，模拟人类在成功的应急管理治疗后复发的情况。我们的数据表明mGluR2的PAMs可用于预防复发。
Cue-induced methamphetamine craving increases after prolonged forced (experimenter-imposed) abstinence from the drug (incubation of methamphetamine craving). Here, we determined whether this incubation phenomenon would occur under conditions that promote voluntary (self-imposed) abstinence. We also determined the effect of the novel mGluR2 positive allosteric modulator, AZD8529, on incubation of methamphetamine craving after forced or voluntary abstinence. We trained rats to self-administer palatable food (6 sessions) and then to self-administer methamphetamine under two conditions: 12 sessions (9-hr/day) or 50 sessions (3-hr/day). We then assessed cue-induced methamphetamine seeking in extinctions test after 1 or 21 abstinence days. Between tests, the rats underwent either forced abstinence (no access to the food- or drug-paired levers) or voluntary abstinence for 19 days (achieved via a discrete choice procedure between methamphetamine and palatable food; 20 trials per day). We also determined the effect of subcutaneous injections of AZD8529 (20 and 40 mg/kg) on cue-induced methamphetamine seeking 1 or 21 days after forced or voluntary abstinence. Under both training and abstinence conditions, cue-induced methamphetamine seeking in the extinction tests was higher after 21 abstinence days than after 1 day (incubation of methamphetamine craving). AZD8529 decreased cue-induced methamphetamine seeking on day 21 but not day 1 of forced or voluntary abstinence. We introduce a novel animal model to study incubation of drug craving and cue-induced drug seeking after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Our data suggest that PAMs of mGluR2 should be considered for relapse prevention.