Abstract: AIM: To investigate the therapeutic effect of vagus nerve stimulation(VNS)on heroin relapse in rats and its possible mechanism.METHODS: The SD rats were trained to self-administer heroin by nose-poking in a daily 4 hours session for consecutive 14 days,to establish an animal model of compulsive drug-seeking and drug-taking. The electrode was implanted into the left vagus nerve and followed by several days recovery,all rats were then trained to 10 daily extinction session and divided into 3 groups:sham control,acute VNS and chronic VNS. The rats in the chronic VNS group were given VNS 2 hours before all extinction and relapse test session,while the rats in the acute VNS group were given VNS 2 hours only before relapse test session. Cue-induced heroin relapse test were measured 24 hours after last extinction session.After relapse testing,c-Fos levels in brain regions of rats were measured by immunofluorescence.RESULTS:Compared with sham group,the active nose-poking of acute VNS and chronic VNS were all significantly decreased (P<0.01). The immunofluorescence results showed that the numbers of c-Fos immuno-positive neurons in central amygdala (Ce) were significantly decreased after acute VNS (P<0.05) or chronic VNS (P<0.01) compared with sham control. However,the numbers of c-Fos immuno-positive neurons in the infralimbic cortex (IL) were significantly increased in both acute VNS and chronic VNS group(P<0.05).CONCLUSION: Acute VNS or chronic VNS may inhibit cue-induced heroin relapse of rats,the possible mechanism might be associate with the alteration of neuron activity in Ce and IL.

Key words: Heroin, Relapse, Vagus nerve stimulation, Central amygdala, Infralimbic cortex