Therapeutic effect of implanted and non-invasive vagus nerve stimulation on heroin-induced anxiety

Substance addiction causes anxiety, which in turn reinforces the maintaining of substance use, resulting in a vicious circle. And this circle is one of the reasons why addiction is so hard to cure. However, there is no treatment involved in addiction-induced anxiety at present. We tested whether VNS (vagus nerve stimulation) can improve heroin-induced anxiety, and made a comparison between nVNS (transcervical vagus nerve stimulation) and taVNS (transauricular vagus nerve stimulation) on therapeutic effect. Mice were subjected to nVNS or taVNS before heroin administration. By observing c-Fos expression in the NTS (nucleus of the solitary tract), we assessed vagal fiber activation. Using the OFT (open field test) and the EPM (elevated cross maze test), we evaluated the anxiety-like behaviors of the mice. Using immuno-fluorescence, we observed the proliferation and activation of microglia in the hippocampus. And ELISA was used to measure the levels of proinflammatory factors in the hippocampus. Both nVNS and taVNS significantly increased the expression of c-Fos in the nucleus of solitary tract, suggesting the feasibility of nVNS and taVNS. The anxiety level of heroin-treated mice was significantly increased, microglia in the hippocampus was significantly proliferated and activated, and the proinflammatory factors (IL-1b, IL-6, TNF-a) in the hippocampus were significantly up-regulated. Crucially, both nVNS and taVNS reversed the above changes caused by heroin addiction.Significance: It was confirmed that the therapeutic effect of VNS on heroin-induced anxiety may be an effective treatment method to break the addiction-anxiety cycle and provides some insights for sub-sequent treatment of addiction.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Substance addiction leads to anxiety, reinforcing the cycle of substance use and making addiction difficult to cure. This study tested whether vagus nerve stimulation (VNS) could improve heroin-induced anxiety and compared the effects of transcervical vagus nerve stimulation (nVNS) and transauricular vagus nerve stimulation (taVNS) on therapeutic outcomes.