RT Journal Article SR Electronic T1 Self-administration of heroin by vapor inhalation in female Wistar rats JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.30.016725 DO 10.1101/2020.03.30.016725 A1 Arnold Gutierrez A1 Jacques D. Nguyen A1 Kevin M. Creehan A1 Michael A. Taffe YR 2020 UL http://biorxiv.org/content/early/2020/03/31/2020.03.30.016725.abstract AB Over the last two decades the United States has experienced a significant increase in the abuse of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. Starting around 2002, there has been an increase in non-medical use of prescription opioids, followed by increased heroin and then fentanyl use. Inhalation has been a common route of administration for opioid drugs, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices, but preclinical reports with inhalation as the model route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin vapor produced slowed tail-withdrawal in male and female rats, demonstrating anti-nociceptive efficacy. Female Wistar rats trained to self-administer heroin vapor exhibited individual preference differences. The most-preferring half of the distribution administered more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 h after last heroin vapor access, consistent with withdrawal signs seen with intravenous self-administration. In sum, these studies show that pharmacological effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin.