The interaction of oxytocin and nicotine addiction on psychosocial stress: an fMRI study

The anxiolytic effect of oxytocin (OXT) on psychosocial stress has been well documented, but the effectiveness under the interference of other factors still requires in-depth research. Previous studies have shown that nicotine addiction interacts with OXT on psychosocial stress on the behavioral level. However, the underlying neural mechanism of interaction between OXT and nicotine addiction on psychosocial stress has not been examined, and we conducted two experiments to reveal it. Firstly, after intranasal administration of randomized OXT or placebo (saline), a group of healthy participants (n = 27) and a group of smokers (n = 26) completed the Montreal Imaging Stress Task (MIST) in an MRI scanner. Secondly, a group of smokers (n = 22) was recruited to complete a transcranial direct current stimulation (tDCS) experiment, in which anodal tDCS was applied on subjects' anterior right superior temporal gyrus (rSTG). In both experiment, subjective stress ratings, salivary cortisol samples and the amount of daily cigarette consumption were obtained from each participant. Analysis of variance were applied on both behavioral and neural data to examine the effects of OXT and nicotine addiction, and correlation analysis were used to examine relationships between neural and behavioral data. In first fMRI experiment, analysis of variance (ANOVA) revealed an interaction of OXT and nicotine addiction on subjective stress. In smokers, OXT failed to suppress the elevation of subjective stress and craving ratings after psychosocial stress. A voxel-wise ANOVA of fMRI data identified an interaction between OXT and nicotine addiction in anterior rSTG, and its functional connectivity with right middle frontal gyrus. Correlations between this functional connectivity and subjective psychosocial stress were also found abnormal in smokers. In second tDCS experiment, we found that under tDCS, OXT successfully suppressed the elevation of subjective stress and craving ratings after stress. In summary, we found that nicotine addiction blocked OXT's anxiolytic on psychosocial stress, which was related to abnormalities in anterior rSTG. By applying anodal tDCS on anterior rSTG, OXT's anxiolytic effect was restored in smokers. These findings will support further development on oxytocin's intervention of psychosocial stress in nicotine addiction, and provides essential information for indicating OXT's effectiveness.