Passive nicotine vapor exposure model in mice reveals translationally relevant dose-dependent cotinine levels and withdrawal behaviors
Abstract
BACKGROUND: Nicotine use disorder and electronic cigarette use remain major public health concerns. While passive vapor exposure systems have been developed in rats, efforts to replicate these approaches in mice have produced inconsistent results, with substantial variability in dosing regimens and limited validation using behavioral and biological markers of nicotine dependence. NEW METHOD: We characterized a passive vapor exposure model in C57BL/6 J mice using nicotine dose-response paradigms and spontaneous withdrawal measures. Mice (N = 69) were exposed to 0, 5, 15, or 50 mg/mL nicotine vapor in a 1:1 PG/VG base for 1 h, followed by serum cotinine measurement. A separate cohort (N = 18) received nicotine or vehicle vapor for two weeks, followed by assessment of somatic signs, locomotion, anxiety-like behavior, body temperature, and thermal nociception 24 h post-cessation. RESULTS: Serum cotinine increased dose-dependently, with males exhibiting higher levels than females at the highest concentration. Both nicotine groups displayed elevated somatic withdrawal scores driven by paw and body tremors. The 15 mg/mL group additionally showed locomotor sensitization and increased nociceptive thresholds. Core body temperature and anxiety-like behavior in the open field were unaffected across all doses. COMPARISON WITH EXISTING METHODS: Our system achieves equivalent or greater cotinine levels within a single 1-hour session across a range of translationally relevant doses, without…
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