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bioRxiv · 10.1101/2025.09.15.676338

Effects of 6-methyl nicotine in middle aged female rats with a history of nicotine vapor self-administration

Taffe, M. A.·Coons, T. R.·Doran, T. A.·Grant, Y.·Vandewater, S. A.
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Abstract

RationaleThe nicotine analog 6-methyl nicotine (6-MN) has recently appeared in non-tobacco nicotine delivery products, including oral pouches and e-cigarette liquids, in an apparent ploy to evade regulation of nicotine by the United States Food and Drug Administration or other public health agencies. Unfortunately, only minimal scientific information on the effects of 6-MN is available. ObjectiveTo determine the extent to which 6-MN produces nicotine-like effects on body temperature, wheel activity and nociception in laboratory rodents. MethodsMiddle-aged (starting at Post Natal Day 425) female Wistar rats were evaluated for rectal temperature, voluntary wheel activity, and nociceptive responses (warm water tail-withdrawal) to subcutaneous injection of nicotine (0.0, 0.8 mg/kg) or 6-methyl nicotine (6-MN; 0.0, 0.4, 0.8 mg/kg). Temperature and nociceptive responses to vapor inhalation of 6-MN [0-30 mg/mL in the propylene glycol (PG) vehicle] were assessed. Finally, the self-administration of 6-MN vapor was compared with nicotine vapor self-administration. Results6-MN decreased rectal temperature, suppressed wheel activity and induced modest nociceptive effects. The magnitude of the effect of 0.8 mg/kg 6-MN and 0.8 mg/kg nicotine were similar across all three assays. Vapor self-administration of 6-MN and nicotine was likewise comparable at a 10 mg/mL concentration. Conclusion6-MN administered by injection or by vapor inhalation produces behavioral and physiological effects that are very similar to those produced by nicotine in rats. It is therefore likely that detrimental health effects of 6-MN will be quite similar to those established for nicotine.

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Taffe, M. A., Coons, T. R., Doran, T. A., Grant, Y., Vandewater, S. A.. 2025-09-21. Effects of 6-methyl nicotine in middle aged female rats with a history of nicotine vapor self-administration. https://doi.org/10.1101/2025.09.15.676338

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