DBS of nucleus accumbens on heroin seeking behaviors in self-administering rats
DBS of nucleus accumbens on heroin seeking behaviors in self-administering rats
复制标题
伏隔核 DBS 对自我给药大鼠海洛因寻求行为的影响
DOI：
10.1016/j.drugalcdep.2012.09.012
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发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Jiang, Jiyao
中科院分区：
文献类型：
--
作者：
Guo, Liemei;Zhou, Hongyu;Jiang, Jiyao
背景：在某些国家，特定脑区的手术消融经常被用来减轻对阿片类药物的心理依赖。然而，由于相关的伦理争议和可能的副作用，消融性脑手术于2004年在中国停止。深部脑刺激 (DBS) 是一种侵入性较小、可逆且可调节的神经调节过程，在药物成瘾研究中被用来减少复发。方法：临床前实验旨在评估伏隔核 (NAc) 的 DBS 对提示和海洛因诱导的药物寻求行为恢复的长期影响。建立海洛因复吸大鼠自我给药模型后，通过同心双极电极对 NAc 核心进行双侧或单侧 DBS 给药。在禁欲期间，每天给予1小时长的连续刺激（130赫兹，100微秒，0-150微安），持续7天。条件线索或小剂量海洛因诱发寻毒行为。结果：75μA和150μA双侧NAc DBS减弱了线索和海洛因诱导的寻毒恢复，右侧NAc的单侧DBS达到了与双侧DBS几乎相当的效果。其他实验表明，DBS 对莫里斯水迷宫任务中的运动活动、空间学习和记忆能力没有长期影响。随后的免疫组织化学测量显示，行为后果与 NAc 中 pCREB 表达的显着增加和 Delta FosB 表达的减少有关。 结论：这些发现表明 NAc DBS 可能是预防海洛因成瘾复发的有效且安全的治疗选择。 (C) 2012 Elsevier Ireland Ltd. 保留所有权利。
Background: Surgical ablation of select brain areas has been frequently used to alleviate psychological dependence on opiate drugs in certain countries. However, ablative brain surgery was stopped in China in 2004 due to the related ethical controversy and possible side effects. Deep brain stimulation (DBS), a less invasive, reversible and adjustable process of neuromodulation, was adopted to attenuate relapses in studies of drug addiction.Methods: Preclinical experiments were designed to assess the long-term effects of DBS of the nucleus accumbens (NAc) on cue- and heroin-induced reinstatement of drug seeking behaviors. After a rat self-administration model of heroin relapse was established, DBS was administered bilaterally or unilaterally to the NAc core through concentric bipolar electrodes. A 1-h long continuous stimulation (130 Hz, 100 mu s, 0-150 mu A) was given daily for 7 days during the abstinence session. Drug seeking behaviors were elicited by conditioned cues or a small dose of heroin.Results: 75 mu A and 150 mu A bilateral NAc DBS attenuated cue- and heroin-induced reinstatement of drug seeking, and unilateral DBS of the right NAc achieved effects almost equivalent to bilateral DBS. Additional experiments showed that DBS had no long-term influence on locomotor activity and spatial learning and retention capabilities in Morris water maze tasks. Subsequent immunohistochemistry measurements revealed that the behavioral consequences were associated with a significant increase in the expression of pCREB and a reduction in the expression of Delta FosB in the NAc.Conclusions: These findings indicate that the NAc DBS could be an effective and safe therapeutic option for preventing relapse to heroin addiction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.