Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats
Non-contingent chronic nicotine exposure procedures have evolved rapidly in recent years, culminating in electronic nicotine delivery systems (ENDS or e-cigarettes) to deliver vaporized drugs to rodents in standard housing chambers.
The aim of the current work was to use ENDS to test concentration-dependent effects of nicotine e-cigarette vapor inhalation on blood-nicotine concentrations, blood-cotinine concentrations, and somatic withdrawal signs over time in rats.
Male Wistar rats were exposed to vapor containing various concentrations of nicotine (20, 40, 80 mg/mL) for 11 days through ENDS, and blood concentrations of nicotine and cotinine, the major proximate metabolite of nicotine, as well as spontaneous and precipitated somatic withdrawal signs, were measured over time (across days of exposure and over hours after termination of vapor exposure).
Exposing male Wistar rats to non-contingent nicotine vapor inhalation through ENDS produces somatic withdrawal symptoms and measurable blood-nicotine and blood-cotinine levels that change according to (1) concentration of nicotine in vape solution, (2) number of days of nicotine vapor exposure, (3) time since termination of nicotine vapor exposure, and (4) relative to the withdrawal signs, whether withdrawal was spontaneous or precipitated (by mecamylamine).
The data presented here provide parameters that can be used as a reasonable starting point for future work that employs ENDS to deliver non-contingent nicotine vapor in rats, although many parameters can and should be altered to match the specific goals of future work.
KeywordsNicotine ENDS E-cigarette Vape Withdrawal Addiction
Funding for this award was provided by the National Institute of Drug Abuse (NIDA) Award R44DA046300 (MC and NWG). This work was supported in part by Merit Review Award no. I01 BX003451 (NWG) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development Service.
Compliance with ethical standards
Conflict of interest
Nicholas W. Gilpin owns shares in Glauser Life Sciences Inc., a company with activities aimed at developing medications for treating mental health disorders; this affiliation had no direct association with the work presented here. Maury Cole is the CEO of LJARI (La Jolla Alcohol Research, Inc.), an organization dedicated to the design and manufacturing of the inhalation systems we purchased.
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