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 ∆ 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 radiotelemetry 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.

Combined Vapor Exposure to THC and Alcohol in Pregnant Rats: Maternal Outcomes and Pharmacokinetic Effects

“…Before and after each vapor inhalation session, core body temperatures were taken from each dam via a rectal thermometer. Previous research suggests that vaporized THC exposure via e-cigarette may reduce core body temperatures during exposure in both male and female rats (Javadi-Paydar et al, 2019;Javadi-Paydar et al, 2018;Nguyen et al, 2016).…”

“…This study used a clinically relevant and effective rodent co-exposure model of e-cigarette THC exposure and alcohol to examine the consequences of prenatal co-exposure. Vapor inhalation paradigms that deliver THC using commercially available e-cigarettes have recently been used in rodents to expose non-pregnant rats (Javadi-Paydar et al, 2019;Javadi-Paydar et al, 2018;Nguyen et al, 2019), but the use of such a model in pregnant rats is more limited (Weimar et al, 2020). To date, a rodent vapor inhalation paradigm for co-exposure to alcohol and cannabis during pregnancy has not been utilized.…”

A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats

“…The primary goal of this study was to establish methods for delivering physiologically and behaviorally significant amounts of heroin to rats via vapor inhalation. To this end we adapted an e-cigarette based inhalation system we have previously shown is effective for the delivery of nicotine (Javadi-Paydar et al, 2019b), THC (Javadi-Paydar et al, 2018a;Nguyen et al, 2016b), cannabidiol (Javadi-Paydar et al, 2019a), methamphetamine (Nguyen et al, 2016a;Nguyen et al, 2017), 3,4-methylenedioxypyrovalerone (MDPV) (Nguyen et al, 2016a) and oxycodone (Nguyen et al, 2019) to rats. Other work has demonstrated anti-nociceptive effects of inhaled oxycodone in male rats (Nguyen et al, 2019) and a preliminary work demonstrates antinociceptive efficacy of inhaled heroin and methadone (Gutierrez et al, 2020) in male and female rats, and reinforcing effects of inhaled heroin in female rats.…”

“…A secondary goal of this study was to determine the parameters necessary for dose control / manipulation within an effective range. As we've shown in prior studies (Javadi-Paydar et al, 2019b;Javadi-Paydar et al, 2018a;Nguyen et al, 2016a;Nguyen et al, 2016b), this can be effected with changes in drug concentration in the vapor vehicle and the duration of inhalation exposure, thus these parameters were under investigation. The final goal was to determine if there are any substantive sex differences in the response to heroin inhalation, see Craft (Craft, 2008) for review.…”

E‐cigarettes, nicotine, the lung and the brain: multi‐level cascading pathophysiology

“…In addition to effects on the central nervous system, nicotine has significant effects on the parasympathetic nervous system, including increased locomotion and decreased body temperature (Javadi‐Paydar et al . 2019). Thus, irrespective of its source, inhaled nicotine produces significant cellular neuronal adaptations.…”