Adult consequences of repeated nicotine vapor inhalation in adolescent rats

Abstract

Introduction: There has been a recent resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Data show almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood in rats. Methods: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from Post-Natal Day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for the self-administration of nicotine vapor (PND 285-395). Plasma levels of nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session. Results: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain or sex differences detected. Adolescent nicotine exposure modestly enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG exposed females for nicotine vapor in a FR5 challenge. Conclusions: The data suggest repeated adolescent nicotine vapor inhalation leads to enhanced liability for nicotine self-administration in adulthood in female rats, but minimal change in spontaneous locomotor behavior.

Adult consequences of repeated nicotine and Δ9-tetrahydrocannabinol (THC) vapor inhalation in adolescent rats

“…In contrast, there were no lasting differences in the baseline wheel activity levels or in the effects of acute nicotine pre-treatment associated with the adolescent exposure to nicotine vapor. This is unlike our prior result for adolescent females exposed to twice daily nicotine vapor inhalation PND 31-40 using the 30 mg/mL concentration (Gutierrez et al, 2022), which suggests the potential importance of dose to the outcome. The addition of nicotine to the THC during adolescent exposure did not significantly modify the impact of the THC.…”

“…Total drug-associated responses increased significantly after the introduction of FR5 and declined again after the restoration of FR1. These are similar to effects previously reported for female rats in a prior study (Gutierrez et al, 2022) and are, together, highly consistent with drug-seeking behavior. This finding supports prior work with different vapor delivery and methodological approaches which also showed nicotine self-administration by vapor inhalation (Cooper, Akers and Henderson, 2021; Lallai et al, 2021; Smith et al, 2020).…”

“…The effect of nicotine, delivered by vapor inhalation, was to suppress wheel activity. This was similar to a suppressive effect of 0.4-0.8 mg/kg nicotine, s.c., injection on wheel activity previously reported (Bryson et al, 1981;Gutierrez et al, 2022). Twice daily adolescent vapor exposure to THC on 10 consecutive days (PND 36-45) produced lasting tolerance the thermoregulatoryeffects of THC in young adulthood, similar to a prior study with rats treated twice daily PND 35-39, 42-46 (Nguyen et al, 2020b).…”

“…This included alterations in hypothermic and anti-nociceptive effects of THC in both sexes, increases food consumption in male rats and increased self-administration of fentanyl in female rats (Nguyen et al, 2020b). Similarly, twice daily vapor exposure to nicotine from PND 31-40 led to lasting alterations in the self-administration of nicotine by vapor inhalation in female, but not male, rats (Gutierrez et al, 2022). Thus, the overall approach of twice-daily adolescent vapor inhalation in brief sessions (30 minutes) using female rats was selected for this investigation.…”

“…The goal of this study was to determine any lasting impact of repeated vapor inhalation of nicotine and THC in adolescent rats on the effects of nicotine and heroin in adulthood. For this, we used an EDDS-based system that has been previously shown effective in delivering nicotine to adult rats (Javadi-Paydar et al, 2019b; Lallai et al, 2021; Montanari et al, 2020), adolescent rats (Gutierrez et al, 2022) and to rat pups in utero (Breit et al, 2022; Hussain, Breit and Thomas, 2022). EDDS-based systems have shown efficacy for nicotine self-administration in rats (Lallai et al, 2021; Smith et al, 2020) and mice (Cooper, Akers and Henderson, 2021; Henderson and Cooper, 2021), and have been used to show that repeated daily exposure to nicotine vapor leads to significant withdrawal following discontinuation in adult rats (Montanari et al, 2020).…”