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

Abstract

Background:The ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy.Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established. Method:We adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.Results: Inhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups. Conclusions:This work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ~50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.

Extended access to fentanyl vapor self-administration leads to addiction-like behaviors in mice: Blood chemokine/cytokine levels as potential biomarkers

“…Fentanyl vapor self-administration caused analgesia, and analgesia positively correlated with the number of fentanyl vapor deliveries. These findings replicate previous studies with vapor-delivered opioids [ 20 , 40 , 41 ] and validate our experimental conditions, indicating that mice achieved sufficient fentanyl levels during self-administration that caused behavioral effects. We did not investigate the development of tolerance to antinociceptive responses because the LgA group escalated their intake in the first hour of the session which would be a confounding factor for the analysis.…”

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

“…THC (100 mg/mL) was suspended in PG at a concentration of 100 mg/mL for vapor inhalation studies and suspended in a 1:1:18 (ethanol:cremophor:saline) vehicle for intraperitoneal injection studies. PG was used as the vapor vehicle for consistency and comparability with our prior reports on the impact of nicotine, THC and heroin vapor inhalation (Gutierrez, Creehan and Taffe, 2021; Javadi-Paydar et al, 2019a; Javadi-Paydar et al, 2019b; Taffe et al, 2021a).…”

“…An e-cigarette based vapor inhalation system (La Jolla Alcohol Research, Inc) which has previously been shown to deliver active doses of THC, cannabidiol, heroin, oxycodone, methamphetamine and nicotine (Gutierrez, Creehan and Taffe, 2021; Javadi-Paydar et al, 2019a; Javadi-Paydar et al, 2019b; Nguyen et al, 2016a; Nguyen et al, 2019) was used for these studies. Vapor was delivered into sealed vapor exposure chambers (152 mm W X 178 mm H X 330 mm L; La Jolla Alcohol Research, Inc, La Jolla, CA, USA) through the use of e-vape controllers (Model SSV-3 or SVS-200; 58 watts, 0.24-0.26 ohms, 3.95-4.3 volts, ∼214 °F; La Jolla Alcohol Research, Inc, La Jolla, CA, USA) to trigger SMOK Baby Beast Brother TFV8 sub-ohm tanks.…”

“…2.3.1 Vapor Inhalation: An e-cigarette based vapor inhalation system (La Jolla Alcohol Research, Inc) which has previously been shown to deliver active doses of THC, cannabidiol, heroin, oxycodone, methamphetamine and nicotine (Gutierrez, Creehan and Taffe, 2021;Javadi-Paydar et al, 2019a;Javadi-Paydar et al, 2019b;Nguyen et al, 2016a;Nguyen et al, 2019) was used for these studies. The apparatus and settings were the same for all drug conditions.…”

Hyperactivity Induced By Vapor Inhalation of Nicotine in Male and Female Rats

“…While some initial studies of ENDS based nicotine exposure resorted to injecting e-cigarette vehicle/nicotine preparations into laboratory rodents (LeSage et al 2016), there has been progress in developing inhalation models for the delivery of several different drugs including cannabinoids (Freels et al 2020; Javadi-Paydar et al 2019a; Nguyen et al 2016b), methamphetamine and other psychomotor stimulants (Marusich et al 2016; Nguyen et al 2016a; Nguyen et al 2017), opioids, including fentanyl (McConnell et al 2021), heroin (Gutierrez et al 2021; Gutierrez et al 2022) and oxycodone (Nguyen et al 2019). Additional work has focused on developing and deploying rat and mouse models of nicotine vapor inhalation (Cooper et al 2021; Echeveste Sanchez et al 2022; Javadi-Paydar et al 2018; Lallai et al 2021; Montanari et al 2020; Roeder et al 2023; Smith et al 2020; Zhu et al 2023).…”