E-cigarette exposure and CDP choline modulate withdrawal- induced anxiety and hormonal levels in rats.

E-cigarette use is rapidly increasing worldwide, yet its impact on mental health and hormonal regulation during withdrawal remains poorly understood. Cytidine-5'-diphosphocholine (CDP-choline) is a neuroprotective compound that may alleviate withdrawal-related disturbances. METHODS: This study evaluated the effects of e-cigarette exposure and subsequent CDP-choline treatment on withdrawal-induced anxiety and hormonal changes in a rat model. Thirty-five adults male Wistar rats were randomly assigned to five groups: control (room air), e-cigarette exposure, e-cigarette exposure + CDP-choline, e-cigarette quitting + CDP-choline, and CDP-choline only. Animals were exposed to e-cigarette vapor for six weeks, followed by either continued exposure at reduced duration or cessation, with CDP-choline administered during the final three weeks. Anxiety-like behavior was assessed using the light-dark box test, and serum nicotine, cotinine, adrenaline, and β-endorphin concentrations were quantified by ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS). RESULTS: Chronic e-cigarette exposure increased serum nicotine, cotinine, adrenaline, and β-endorphin levels compared with controls, and was associated with withdrawal-induced anxiety. CDP-choline treatment reduced serum nicotine and cotinine concentrations, normalized adrenaline and β-endorphin levels, and improved behavioral outcomes, as indicated by increased time spent in the light chamber and reduced stretching frequency. CONCLUSION: CDP-choline mitigates the biochemical and behavioral disturbances associated with e-cigarette exposure and withdrawal, highlighting its potential as a therapeutic strategy for nicotine dependence. Future studies incorporating pharmacokinetic profiling, long-term efficacy assessment, and inclusion of female subjects are warranted to further clarify its mechanisms and clinical applicability.