Vagus nerve is essential for the anxiolytic effect of YL-IPA08, a potent ligand for the translocator protein (18 kDa).

The vagus nerve serves as a key neural pathway modulating parasympathetic activity, which plays a critical role in mood regulation and has been implicated in anxiety and depression. The translocator protein (18 kDa, TSPO) ligand YL-IPA08 has demonstrated consistent anxiolytic effects in animal studies. Using lipopolysaccharide (LPS)- or cefaclor-induced anxiety models in adult mice with or without vagotomy, we investigated the involvement of the vagus nerve in mediating the effects of YL-IPA08 and its underlying mechanisms. As anticipated, chronic YL-IPA08 administration significantly reversed anxiety-related behaviors induced by LPS or antibiotic exposure, an effect that was attenuated by vagotomy. Furthermore, vagotomy impaired YL-IPA08's ability to counteract cefaclor-induced microglial activation and inflammatory responses in the prefrontal cortex (PFC). The present study shows that YL-IPA08 exerts significant anxiolytic effects, which are associated with the vagus nerve signaling pathway, suggesting that the vagus nerve may be involved in partial regulation of these effects.