Neurometabolic alterations in the nucleus accumbens of smokers assessed with 1H magnetic resonance spectroscopy: The role of glutamate and neuroinflammation

다국어 초록 (Multilingual Abstract)

Tobacco use is one of the leading causes of premature death and morbidity worldwide. For smokers trying to quit, relapse rates are high, even after prolonged periods of abstinence. Recent findings in animal models highlight the role of alterations in glutamatergic projections from the prefrontal cortex onto the nucleus accumbens (NAc) in relapse vulnerability. Moreover, inflammatory responses in the NAc have been reported during withdrawal.
A novel proton magnetic resonance spectroscopy (1H‐MRS) protocol was applied in humans to measure molar concentrations for glutamate, its sum with glutamine (Glx), and myoinositol plus glycine (mI + Gly) in the NAc (19 smokers, 20 matched controls). Smokers were measured at baseline and during withdrawal and satiation.
No difference between groups or smoking states was found for glutamate or Glx, but, in smokers, stronger craving and more severe nicotine dependence were associated with lower baseline glutamate and Glx levels, respectively. Interestingly, mI + Gly concentrations were higher during withdrawal than baseline and correlated negatively with nicotine dependence severity and pack years of smoking.
The lack of glutamatergic changes between groups and smoking states may imply that glutamate homeostasis is not significantly altered in smokers or that changes are too small for detection by 1H‐MRS. Moreover, the observed increase in mI + Gly may imply that neuroinflammatory processes occur in the NAc during nicotine withdrawal. These findings shed light on neurobiological relapse mechanisms in smokers and may provide the opportunity to develop more effective treatment options targeting the glutamate and neuroinflammation system.
With a novel proton magnetic resonance spectroscopy protocol, absolute molar concentrations for glutamate and its sum with glutamine (Glx) and myoinositol were measured in the human nucleus accumbens (NAc) of 19 smokers in different smoking states and in 20 controls. In smokers, lower baseline glutamate and Glx levels were associated with stronger craving and more severe nicotine dependence, respectively, providing preliminary evidence for perturbed glutamate homeostasis in the NAc in heavy smokers. Myoinositol concentrations were higher after 24 h of withdrawal than baseline and correlated negatively with nicotine dependence severity and pack‐years of smoking, possibly implying that neuroinflammatory processes occur in the NAc during nicotine withdrawal.