Neural Basis Of Intranasal Oxytocin Decreasing Stress-induced Cigarettes Craving In Smokers

Stress plays a key role in the initiation, maintenance and relapse of nicotine craving, as well as in damage of endogenous oxytocin system by weakening social emotional connection leading to tobacco abuse. The underlying neural basis of the effects of oxytocin (OT) on cigarettes craving by modulating stress are of great importance. However, it remains a considerably hard and unproved issue.In present study, we investigated the neural rationale of this issue in abstinent smokers using a psychosocial stress procedure with exogenous OT nasal spray.First of all, we tested the effectiveness of the Montreal Imaging Stress Task(MIST) in 25 male smokers. Then, we explored whether OT could reduce stress-induced craving in 22 male smokers. Finally, we used functional magnetic resonance imaging (fMRI) to ascertain the OT effects related brain regions while 35 nicotine-dependent men were exposed to psychosocial stress induced by MIST paradigm 30 minutes after the application of either 24 IU OT or placebo, scanning resting state fMRI pre-MIST and post-MIST as well. In addition to subject ratings of stress and nicotine craving, emotion as well as cortisol and Tobacco Craving Questionnaire were measured in pretest and post-test.Stress-induced craving could be successfully induced by MIST paradigm.Positive correlation between increased craving and stress. Reduction of craving as well as withdrawal symptoms such as negative emotions and anxiety following OT spray. Reduction of craving was associated with activation of cingulum which included anterior cingulate cortex (ACC) and middle cingulate cortex (MCC), whole brain functional connection (FC) analysis revealed that significant augment of FC between right cingulum and right inferior triangle area of Frontal (IF_tri_R) such as right orbitofrontal cortex (OFC).Our results indicated that a mere 24 IU dose nasal spray of OT down-regulating the craving in 2 hour-abstinent male smokers, which might be related to the enhancement inhibition of right inferior triangle area of Frontal (IF_tri_R) on the abnormal activation of the right cingulum. Improvement of the brain's executive control abilities perhaps alleviate stress-induced cigarette craving and withdrawal negative emotions, positive correlation was found to between them.This study explored the physical and mental effects of neuropeptide OT on stress-induced cigarette craving for the first time, providing theoretical guidance and preliminary clinical basis for finding more effective therapeutic targets and oxytocin-based therapeutic on smoking addiction treatment.