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Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats

by Huifen Liu, Yijun Liu, Jing Yu, Miaojun Lai, Huaqiang Zhu, Anna Sun, Weisheng Chen and Wenhua Zhou


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 14 days 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 (30 Hz, pulse width of 0.5 ms, 0.5 mA (low-intensity) or 1 mA (high-intensity); 30 s on, 5 min off; 10 continuous cycle per day) or false stimulation during extinction training. We found that such vagus nerve stimulation significantly inhibited heroin priming (0.25 mg/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.


► Stimulation of vagus nerve inhibits the heroin seeking induced by cue or heroin. ► Electric stimulation decreases the expression of Fos protein. ► Electric stimulation increases the expression of pCREB protein.

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