Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Drug Alcohol Depend. 2013 Apr 1;129(1-2):70-81. doi: 10.1016/j.drugalcdep.2012.09.012. Epub 2012 Oct 11.
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.
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 μs, 0-150 μA) was given daily for 7 days during the abstinence session. Drug seeking behaviors were elicited by conditioned cues or a small dose of heroin.
75 μA and 150 μA 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 ΔFosB in the NAc.
These findings indicate that the NAc DBS could be an effective and safe therapeutic option for preventing relapse to heroin addiction.
在某些国家，外科选择性脑区消融术已被频繁用于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，消融性脑外科手术于 2004 年在中国停止。脑深部刺激（DBS）是一种侵袭性较小、可逆和可调节的神经调节过程，被用于减轻药物成瘾研究中的复发性。
设计了临床前实验来评估伏隔核（NAc）DBS 对线索和海洛因诱导的药物寻求行为复发起长期作用。在建立海洛因复发性大鼠自身给药模型后，通过同心双极电极对 NAc 核双侧或单侧给予 DBS。在禁欲期每天给予 1 小时连续刺激（130 Hz，100 μs，0-150 μA）持续 7 天。通过条件线索或小剂量海洛因诱发药物寻求行为。
75 μA 和 150 μA 双侧 NAc DBS 减弱了线索和海洛因诱导的药物寻求复燃，单侧右侧 NAc DBS 几乎与双侧 DBS 达到等效效果。额外的实验表明，DBS 对运动活动和空间学习和保留能力没有长期影响，在 Morris 水迷宫任务中。随后的免疫组织化学测量显示，行为后果与 NAc 中 pCREB 表达的显著增加和 ΔFosB 表达的减少有关。
这些发现表明，NAc DBS 可能是预防海洛因成瘾复发的一种有效且安全的治疗选择。
