EFFECTS OF SMOKING CUES ON CORTICOSTRIATAL GLUTAMATE LEVELS IN NON-SMOKERS

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 1.Cortese BM, Uhde TW, Brady KT, McClernon FJ, Yang QX, Collins HR, et al. The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults. Psychiatry Res 2015;234:321–7. 2.Lin X, Deng J, Shi L, Wang Q, Li P, Li H, et al. Neural substrates of smoking and reward cue reactivity in smokers: a meta-analysis of fMRI studies. Translational Psychiatry [Internet] 2020 [cited 2023 Dec 13];10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078287/. 3.Boormans AJMG, Dieleman J, Kleinjan M, Otten R, Luijten M. Environmental Tobacco Smoke Exposure and Brain Functioning Associated with Smoking Cue-Reactivity and Inhibitory Control in Nonsmoking Adolescents. European Addiction Research 2021;27:341–50. 4.Deweese MM, Codispoti M, Robinson JD, Cinciripini PM, Versace F. Cigarette cues capture attention of smokers and never-smokers, but for different reasons. Drug Alcohol Depend 2018;185:50–7. 5.Versace F, Minnix JA, Robinson JD, Lam CY, Brown VL, Cinciripini PM. Brain reactivity to emotional, neutral and cigarette-related stimuli in smokers. Addict Biol 2011;16:296–307. 6.Abdullah M, Huang LC, Lin SH, Yang YK. Dopaminergic and glutamatergic biomarkers disruption in addiction and regulation by exercise: a mini review. Biomarkers. 2022;27:1–13.