Linking oxytocin to nicotine dependence: An experimental study of the brain, behavior, and gut microbiota in rats

Oxytocin (OXT) is a hypothalamic neuropeptide, and numerous studies have indicated that exposure to addictive substances, such as opioids, cocaine, etc., can result in decreased function of the OXT system. The study also found that OXT can reduce addictive behavior for certain drugs, including methamphetamine, alcohol, and cocaine, suggesting a close relationship between the OXT system and drug abuse. Although nicotine is the main addictive substance in tobacco, its interaction with the OXT system is unknown and requires further study. Therefore, OXT levels in plasma and brain regions associated with addiction were measured by enzyme-linked immunosorbent assay (ELISA) using chronic nicotine administration via a slow-release pump. In addition, the effects of OXT injection on nicotine self-administration behavior, motor activity, and intestinal microbiota in rats were examined by nicotine self-administration experiment, open field experiment, and 16S sequencing experiment. By depleting gut microbiota with oral antibiotics, this study aims to investigate whether gut microbiota mediates oxytocin effect on the nicotine self-administration behavior in rats. This study shows that chronic nicotine administration can reduce OXT levels in plasma and brain regions such as the paraventricular nucleus (PVN), ventral tegmental area (VTA), and caudate putamen (CPU). OXT at a dose of 1.0 mg/kg significantly reduced the number of nicotine infusions and the abundance of Lactobacillus in rats. Notably, our findings indicate that other mechanisms besides gut microbes are involved in the effect of peripheral OXT administration on the inhibition of nicotine self-administration.