Effect of acute nicotine withdrawal and oral nicotine substitution treatment on insular glutamine concentration determined by proton magnetic resonance spectroscopy

Introduction: The insular cortex is thought to play an important role in the pathophysiology of tobacco dependence. However, the effects of acute nicotine withdrawal and following nicotine substitution on neurometabolic changes in the insular cortex are still unknown.

Method: A total of 14 male smokers and 10 male nonsmokers were investigated by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject. Furthermore, craving, withdrawal symptoms, CO levels was assessed in all participating subjects.

Results: In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers did not show any metabolic changes over all three phases (p > 0.05).

Conclusions: These results indicate that acute nicotine withdrawal produces a neurometabolic reaction pattern in the insular cortex that is partly reversed by oral nicotine. The molecular mechanism and clinical significance of this insular neurometabolic changes merit further investigation.