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

Abstract

Background: Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as Δ 9-tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS. Methods: Male Sprague-Dawley rats (N=8) were prepared with radio telemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL). Results: Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats. Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity). Conclusions: These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.

Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats

“…nicotine self-administration in male Wistar rats ). More recent work used ENDS to show that nicotine vapor inhalation increases spontaneous locomotion and reduces body temperature in male Sprague-Dawley rats, and that these effects are blocked by systemic injection of mecamylamine (Javadi-Paydar et al 2019).…”

“…Recently, we began using ENDS to deliver vaporized drugs to rodents in standard housing chambers. This method has been used to administer vaporized Δ9-tetrahydrocannabinol (THC; Nguyen et al 2016aNguyen et al , 2018Javadi-Paydar et al 2018, opiates (Vendruscolo et al 2018), stimulants (Nguyen et al 2016b(Nguyen et al , 2017, nicotine (Javadi-Paydar et al 2019), or combinations of these drugs (Javadi-Paydar et al 2019). ENDS nicotine inhalation produces behavioral and physiological effects in rats, such as increases in spontaneous locomotor activity and decreases in body temperature (Javadi-Paydar et al 2019).…”

“…This method has been used to administer vaporized Δ9-tetrahydrocannabinol (THC; Nguyen et al 2016aNguyen et al , 2018Javadi-Paydar et al 2018, opiates (Vendruscolo et al 2018), stimulants (Nguyen et al 2016b(Nguyen et al , 2017, nicotine (Javadi-Paydar et al 2019), or combinations of these drugs (Javadi-Paydar et al 2019). ENDS nicotine inhalation produces behavioral and physiological effects in rats, such as increases in spontaneous locomotor activity and decreases in body temperature (Javadi-Paydar et al 2019). Here, we chronically exposed male Wistar rats to different concentrations of nicotine, then we measured nicotine and cotinine (the major proximate metabolite of nicotine [Benowitz 1984] often used as a biomarker for nicotine exposure [Perez-Stable et al 1995]) blood concentrations, and physical (spontaneous and precipitated) withdrawal symptoms over time (between and within sessions).…”

Vapor inhalation of cannabidiol (CBD) in rats

“…similar methods to evaluate body temperature responses (Taffe et al, 2015). The inhalation study used an ecigarette based vapor inhalation approach which has now been shown effective for delivering physiologically relevant doses of sufentanil, THC, methamphetamine, the substituted cathinones ("bath salts") MDPV and 4-MMC as well as nicotine to rats (Javadi-Paydar et al, 2019;Nguyen et al, 2016a;Nguyen et al, 2016b;Vendruscolo et al, 2018).…”

Acute exposure to nicotine vapor causes short-term increases in impulsive choice in rats

“…Research investigating the effects of nicotine vapor inhalation from electronic cigarettes (e-cigarettes) is beginning to demonstrate that consumption of nicotine using this novel nicotine delivery system can have detrimental effects on human health that are both similar and new when compared to traditional smoking (Callahan-Lyon, 2014;Chun, Moazed, Calfee, Matthay, & Gotts, 2017). However, pre-clinical studies linking nicotine vapor consumption from e-cigarettes to changes in the brain and behavior are limited (Javadi-Paydar, Kerr, Harvey, Cole, & Taffe, 2019;Smith et al, 2015). This is concerning, as e-cigarette vaping in adolescents has now surpassed conventional cigarette smoking, with use increasing from 1.5% in 2011 to 20.8% in 2018 (Gentzke et al, 2019).…”