Delivery of nicotine aerosol to mice via a modified electronic cigarette device

Abstract

Background Although both men and women use e-cigarettes, most preclinical nicotine research has focused on its effects in male rodents following injection. The goals of the present study were to develop an effective e-cigarette nicotine delivery system, to compare results to those obtained after subcutaneous (s.c.) injection, and to examine sex differences in the model. Methods Hypothermia and locomotor suppression were assessed following aerosol exposure or s.c. injection with nicotine in female and male mice. Subsequently, plasma and brain concentrations of nicotine and cotinine were measured. Results Passive exposure to nicotine aerosol produced concentration-dependent and mecamylamine reversible hypothermic and locomotor suppressant effects in female and male mice, as did s.c. nicotine injection. In plasma and brain, nicotine and cotinine concentrations showed dose/concentration-dependent increases in both sexes following each route of administration. Sex differences in nicotine-induced hypothermia were dependent upon route of administration, with females showing greater hypothermia following aerosol exposure and males showing greater hypothermia following injection. In contrast, when they occurred, sex differences in nicotine and cotinine levels in brain and plasma consistently showed greater concentrations in females than males, regardless of route of administration. Discussion In summary, the e-cigarette exposure device described herein was used successfully to deliver pharmacologically active doses of nicotine to female and male mice. Further, plasma nicotine concentrations following exposure were similar to those after s.c. injection with nicotine and within the range observed in human smokers. Future research on vaped products can be strengthened by inclusion of translationally relevant routes of administration.

OpenVape: An Open-Source E-Cigarette Vapor Exposure Device for Rodents

“…Although it is difficult to compare CPP results between studies because of methodological differences, the change in preference of our highest dose duration (8-min puff exposure) appears to be roughly equivalent with those found with subcutaneous injections of 0.6 mg/kg ( Torres et al, 2008 ). This is consistent with the plasma nicotine levels observed at the longest exposure duration, with levels roughly equivalent to the peak concentrations seen with subcutaneous injections of 0.5 mg/kg ( Lefever et al, 2017 ). These levels are also akin to those seen in adult cigarette smokers ( Matta et al, 2007 ).…”

“…Simpler designs have also been implemented. An e-cigarette exposure apparatus by Lefever et al (2017) is most similar to OV in its low-cost and simple construction; however, similar to the previously described device, it makes use of an atomizer for vapor generation, therefore limiting its use to e-liquids. OV can be used with any vaporizer and has been used with both pod devices and cannabis flower vaporizers.…”

“…Current commercially available nicotine vapor exposure apparatuses (e.g., DSI Buxco, SCIREQ inExpose, LJARI eVape) are prohibitively expensive and require proprietary hardware and software to operate, thereby limiting their accessibility and versatility. This has led others to create customized alternatives ( Manwell et al, 2014 ; Liu et al, 2016 ; Nguyen et al, 2016 ; Hage et al, 2017 ; Lefever et al, 2017 ; Hilpert et al, 2019 ). However, these alternatives are still very expensive, complicated to construct, and are not always open-source.…”

Effects of Nicotine and THC Vapor Inhalation Administered by An Electronic Nicotine Delivery System (ENDS) in Male Rats

“…Interestingly, a 0.8 mg/kg dose of nicotine injected, s.c., reduced activity rates. Hypothermia is produced by parenteral injection of nicotine in rats (Levin et al 2003) as is hyperlocomotion (Bryson et al 1981;Clemens et al 2009;Green et al 2003) and decreased body temperature was observed after vapor inhalation of nicotine in mice (Lefever et al 2017). Furthermore, the effects of inhaled nicotine in this study were shown to be mediated by the nicotinic acetylcholine receptor (nAChR) since they were attenuated (temperature) or blocked entirely (locomotion) by pre-treatment with mecamylamine ( Figure 3).…”

Effects of nicotine and THC vapor inhalation administered by an electronic nicotine delivery system (ENDS) in male rats

“…There are as yet relatively few studies of the effects of ENDS in rodent models, however, recent studies showed e-cigarette based vapor inhalation of nicotine in mice reduced body temperature and locomotor activity (Lefever et al, 2017) and increased platelet activity (Qasim et al, 2018), which together demonstrate the feasibility of the approach. The paucity of models is underlined by the fact that several recent studies have resorted to parenteral injection of e-cigarette refill liquids to determine effects in rats (Bunney et al, 2018;El Golli et al, 2016;Golli et al, 2016;Harris et al, 2015;LeSage et al, 2016).…”