Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Str., Ningbo 315010, Zhejiang Province, PR China.
Neurosci Lett. 2011 Apr 20;494(1):70-4. doi: 10.1016/j.neulet.2011.02.059. Epub 2011 Mar 6.
Vagus nerve stimulation has been used for the treatment of neuropsychiatric disorders, such as epilepsy. However, little is known whether it is also effective for the treatment of heroin dependence, in particular for relapse to heroin seeking. In the present study, we investigated the effects of vagus nerve stimulation on reinstatement (relapse) of heroin-seeking behavior induced by heroin priming or heroin-associated cues. The rats were trained for heroin self-administration for 14days and followed by extinction training in which heroin was replaced by saline and heroin-associated cues were turned off. In addition, animals were also received daily electric stimulation of vagus nerve (30Hz, pulse width of 0.5ms, 0.5mA (low-intensity) or 1mA (high-intensity); 30s on, 5min off; 10 continuous cycle per day) or false stimulation during extinction training. We found that such vagus nerve stimulation significantly inhibited heroin priming (0.25mg/kg, s.c.) - or heroin-associated conditioned cue-induced reinstatement of drug-seeking behavior, when compared to false stimulation control. Further, such a behavioral inhibition was correlated to a reduction in the expression of FosB and an increase in the expression of phosphorylation of cAMP response element binding protein (p-CREB) in nucleus accumbens. The data suggest that vagus nerve stimulation may inhibit heroin- or heroin cue-induced relapse, possibly by regulation of the expression of Fos and CREB in nucleus accumbens.
迷走神经刺激已被用于治疗神经精神疾病，如癫痫。然而，对于迷走神经刺激是否也能有效治疗海洛因依赖，特别是对海洛因寻求的复吸，知之甚少。在本研究中，我们研究了迷走神经刺激对海洛因催瘾或海洛因相关线索诱导的觅药行为复吸的影响。大鼠接受了 14 天的海洛因自我给药训练，随后进行了消退训练，在消退训练中，海洛因被盐水取代，海洛因相关线索被关闭。此外，动物还在消退训练期间接受每日迷走神经电刺激（30Hz，脉冲宽度 0.5ms，0.5mA（低强度）或 1mA（高强度）；30s ON，5min OFF；每天 10 个连续周期）或假刺激。我们发现，与假刺激对照相比，这种迷走神经刺激显著抑制了海洛因催瘾（0.25mg/kg，皮下注射）或海洛因相关条件线索诱导的觅药行为复吸。进一步的，这种行为抑制与伏隔核中 FosB 表达减少和 cAMP 反应元件结合蛋白磷酸化（p-CREB）表达增加相关。数据表明，迷走神经刺激可能通过调节伏隔核中 Fos 和 CREB 的表达来抑制海洛因或海洛因线索诱导的复吸。
