EFFECTS OF SMOKING CUES ON CORTICOSTRIATAL GLUTAMATE LEVELS IN NON-SMOKERS
Authors: Abdullah *Muhammad , Lin Shih-Hsien , Huang Li-Chung , Tseng Huai-Hsuan , Chen Po See , Yang Yen Kuang 
Published: February 2025

Abstract

Background
Smoking cues attract the attention of both smokers and non-smokers [1–4]. Neurophysiological studies have shown an increase in brain electrical activity, and functional magnetic resonance imaging studies have reported activations for smoking cues in the reward-associated areas, mainly the anterior cingulate cortex (ACC) and striatum, in both smokers and non-smokers [1–5]. The molecular mechanism in humans remains unknown. Previously, animal studies have extensively investigated the increase in glutamatergic tone in cue-associated reward areas in addicted animal models [6].

Aims & Objectives
This study explores glutamatergic modulations in non-smokers in response to smoking cues, aiming to understand the neurochemical basis of cue-induced phenomena.

Methods
A total of 49 healthy non-smoking male participants were recruited. Proton magnetic resonance spectroscopy (MRS) scans were conducted in the ACC and striatum using a 3.0 Tesla MRI scanner. Two MRS sessions, each lasting 5:4 minutes, were conducted in both areas, with the initial session aimed at establishing baseline glutamate levels (neutral images), and the subsequent session focused on measuring the change in response to smoking cues (smoking images). The order of functional MRS scans was ACC-Striatum-Striatum-ACC to minimize the shimming effect during voxel switching. Paired sample t-tests were performed to quantify glutamatergic changes for smoking cue.

Results
Pairwise analyses indicated a significant increase in Glx (glutamate + glutamine) (p = 0.008) following exposure to smoking cues in the ACC. Additionally, there was a significant elevation in glutamine levels in the ACC (p = 0.001). However, no statistically significant alterations were observed in glutamatergic metabolites in the striatum in response to smoking cues.

Conclusion
This study noted an elevation in glutamatergic tone in the ACC when healthy non-smokers were exposed to smoking cues, emphasizing the role of glutamatergic neurometabolites in cue-induced phenomena in humans.

References
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