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

Abstract

BackgroundThe 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. MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effectsin 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. ResultsInhalation 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 min produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 min produced robust effects across all endpoints and groups. ConclusionsThis 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 min. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.