High Impulsivity Predicts Relapse to Cocaine-Seeking After Punishment-Induced Abstinence
High Impulsivity Predicts Relapse to Cocaine-Seeking After Punishment-Induced Abstinence
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DOI：
10.1016/j.biopsych.2008.12.008
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发表时间：
2009-05-15
影响因子：
10.6
通讯作者：
Everitt, Barry J.
中科院分区：
文献类型：
--
作者：
Economidou, Daina;Pelloux, Yann;Everitt, Barry J.
背景：复吸是可卡因成瘾的一个标志性特征，也是治疗策略的一个主要挑战。人类的研究表明冲动和增加易感性relations.Methods之间的联系：大鼠筛选高（HI）和低冲动（LI）的5选择系列反应时间任务。HI和LI大鼠接受训练，以自我管理的可卡因下寻求-服用连锁计划：寻求杠杆的反应导致介绍的服用杠杆，响应后，导致可卡因的强化。在建立了稳定的反应之后，引入了间歇性的惩罚时间表：完成寻找链接导致随机呈现采取杠杆或轻微的脚震。这导致了可卡因寻求接近禁欲的逐步减少。在惩罚后7天评估复发，在此期间，对寻求杠杆的反应导致可卡因相关刺激的呈现（即，结果：HI和LI组动物在寻求惩罚的单一阶段后，可卡因寻求反应显著恢复。然而，在第二个惩罚阶段后，只有HI大鼠重新启动抑制寻求反应和复发，这种效果是由先前延长可卡因访问促进。在一项初步研究中，我们发现，选择性去甲肾上腺素再摄取抑制剂，托莫西汀，一种药物，以减少冲动，防止恢复可卡因seeking.Conclusions：冲动约会前药物滥用增加的易感性戒毒后复发。针对冲动性的药物可能作为预防复发和促进禁欲的治疗干预措施。
Background: Relapse is a hallmark feature of cocaine addiction and a main challenge for treatment strategies. Human studies indicate a link between impulsivity and increased susceptibility to relapse.Methods: Rats were screened for high (HI) and low impulsivity (LI) on the 5-choice serial reaction time task. The HI and LI rats were trained to self-administer cocaine under a seeking-taking chained schedule: responses on the seeking lever resulted in presentation of the taking lever, responding upon which resulted in cocaine reinforcement. After the establishment of stable responding, an intermittent punishment schedule was introduced: completion of the seeking link resulted in the random presentation of either the taking lever or a mild footshock. This resulted in a progressive decrease in cocaine-seeking approaching abstinence. Relapse was assessed 7 days after punishment, during which responding on the seeking lever resulted in the presentation of the cocaine-associated stimuli (i.e., in the absence of cocaine or footshock).Results: The HI and LI animals significantly reinstated the cocaine-seeking response after a single phase of seeking punishment. However, after a second punishment phase only the HI rats reinitiated suppressed seeking responses and relapsed, an effect that was facilitated by prior extended cocaine access. In a preliminary study we found that the selective noradrenaline reuptake inhibitor, atomoxetine, a drug known to reduce impulsivity, prevented the reinstatement of cocaine-seeking.Conclusions: Impulsivity pre-dating drug abuse increases the susceptibility to relapse after abstinence. Medications targeting impulsivity might have utility as treatment interventions for relapse prevention and the promotion of abstinence.