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A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-10-03 , DOI: 10.1101/2020.09.03.281857
Arnold Gutierrez , Kevin M. Creehan , Michael A. Taffe

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.

中文翻译:

递送海洛因的蒸气暴露方法会改变雌性和雄性大鼠的伤害感受,体温和自发活动

背景:与非医疗用途的阿片类药物相关的持续危机使了解阿片类药物成瘾的危险因素,阿片类药物暴露的行为和神经生物学后果以及寻找潜在的治疗途径变得越来越重要。临床前的啮齿动物模型几十年来一直是增进对阿片类药物后果的认识的关键,但主要限于通过注射或口服给药的药物。吸入对于许多人类使用者而言是重要的途径,但尚未确立。方法:我们采用了一种基于电子烟的暴露系统,该系统先前显示出可以有效地向大鼠输送其他药物,并可以输送海洛因蒸气。在雄性和雌性Sprague-Dawley大鼠中,使用温水测定抗伤害感受和植入式无线电遥测系统评估体温和自发活动率的变化,评估了体内效应。结果:在丙二醇(PG)介质中吸入100 mg / mL海洛因产生的蒸气显着减慢了从52°C水浴中抽出尾巴的速度,双相改变的活动以及雌雄大鼠的体温升高。吸入海洛因50 mg / mL持续15分钟可产生显着效果,这是药效的下限;而吸入海洛因100 mg / mL 30分钟可在所有终点和所有组产生强效作用。结论:这项工作表明,电子烟设备可向大鼠提供精神活性剂量的海洛因,使用〜50-100 mg / mL的浓度和15-30分钟的吸入时间。该技术可能对评估吸入的海洛因和其他阿片类药物的健康后果很有用。
更新日期:2020-10-04
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