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Glutamate Dynamics in Reward-associated Areas During Smoking Cue Exposure in Male Smokers: A Proton Magnetic Resonance Spectroscopy Study.

M. Abdullah,Shih-Hsien Lin,Li-Chung Huang,Ren-Yi Lin,Po-See Chen,Huai-Hsuan Tseng,Yen-Kuang Yang

Published 2025 in Journal of addiction medicine

ABSTRACT

OBJECTIVES Functional magnetic resonance imaging studies have shown that smoking cues activate reward-related brain regions, with activation intensity increasing with smoking addiction severity. A recent study on cocaine addiction reported increased striatal glutamatergic tone in response to cocaine-associated cues; however, the role of glutamate in smoking cue-induced brain activation and its relationship with addiction severity remain unclear. METHODS This study investigated glutamate modulation in the anterior striatum and dorsal anterior cingulate cortex (ACC) of male participants, comprising smokers (n = 38) and healthy controls (n = 48), exposed to smoking cues. Magnetic resonance spectroscopy (MRS) was used to measure glutamate levels at baseline (neutral images) and during smoking cue (smoking images) presentation. RESULTS A mixed-model ANOVA followed by post hoc paired t tests revealed a significant increase in striatal glutamate levels in smokers exposed to smoking cues, whereas no changes were observed in controls. This effect on striatal glutamate in smokers remained significant after controlling for age. No significant changes were observed in the ACC in either smokers or controls. Although a positive association trend was found between smoking severity, as measured by the Fagerström Test for Nicotine Dependence (FTND) scores, and striatal cue-induced glutamate changes, it was not statistically significant. CONCLUSIONS These findings suggested that smoking cue-induced increases in striatal glutamate tone may reflect the neurochemical mechanisms underlying cue-induced phenomena in humans.

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