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Female rats self-administer heroin by vapor inhalation
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-10-14 , DOI: 10.1101/2020.03.30.016725 Arnold Gutierrez , Jacques D. Nguyen , Kevin M. Creehan , Michael A. Taffe
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-10-14 , DOI: 10.1101/2020.03.30.016725 Arnold Gutierrez , Jacques D. Nguyen , Kevin M. Creehan , Michael A. Taffe
Over the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the 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 or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained 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 hours after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive 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 or other opioids.
中文翻译:
雌性大鼠通过蒸气吸入自我施用海洛因
在过去的二十年中,美国在医学和非医学领域使用阿片类药物的人数显着增加,导致与阿片类药物有关的药物过量和死亡人数达到创纪录的水平。在2002年前后,非阿片类药物的非医疗用途开始增加,随后是海洛因使用的增加,最近是芬太尼的使用。吸入是阿片类药物的常见给药途径,有文献记载的历史可追溯到地中海古代,直到现代与电子烟设备一起使用。不幸的是,使用吸入作为给药途径的临床前研究仍然相对较少。进行该研究以确定电子烟蒸气吸入海洛因对大鼠的功效。非偶然性接触海洛因或美沙酮蒸气在雄性和雌性大鼠中产生抗伤害感受功效。训练雌性大鼠自给海洛因蒸气。当蒸汽媒介物中海洛因的浓度降低并且用阿片受体拮抗剂纳洛酮预处理时,分布中最优选的一半获得了更多的蒸汽增强剂。蒸汽自给的海洛因的抗伤害感受作用与静脉自给的海洛因具有一定的镇痛作用。最后,上一次海洛因蒸气进入后24-48小时,焦虑样行为增加,与静脉内自行给药后观察到的戒断症状一致。总之,这些研究表明,使用电子烟技术通过蒸气吸入在大鼠中产生了海洛因的奖励和抗伤害感受作用。重要的,
更新日期:2020-10-16
中文翻译:
雌性大鼠通过蒸气吸入自我施用海洛因
在过去的二十年中,美国在医学和非医学领域使用阿片类药物的人数显着增加,导致与阿片类药物有关的药物过量和死亡人数达到创纪录的水平。在2002年前后,非阿片类药物的非医疗用途开始增加,随后是海洛因使用的增加,最近是芬太尼的使用。吸入是阿片类药物的常见给药途径,有文献记载的历史可追溯到地中海古代,直到现代与电子烟设备一起使用。不幸的是,使用吸入作为给药途径的临床前研究仍然相对较少。进行该研究以确定电子烟蒸气吸入海洛因对大鼠的功效。非偶然性接触海洛因或美沙酮蒸气在雄性和雌性大鼠中产生抗伤害感受功效。训练雌性大鼠自给海洛因蒸气。当蒸汽媒介物中海洛因的浓度降低并且用阿片受体拮抗剂纳洛酮预处理时,分布中最优选的一半获得了更多的蒸汽增强剂。蒸汽自给的海洛因的抗伤害感受作用与静脉自给的海洛因具有一定的镇痛作用。最后,上一次海洛因蒸气进入后24-48小时,焦虑样行为增加,与静脉内自行给药后观察到的戒断症状一致。总之,这些研究表明,使用电子烟技术通过蒸气吸入在大鼠中产生了海洛因的奖励和抗伤害感受作用。重要的,