Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake

Amanda L Sharpe, Laci R Liter, Darius Donohue, Kelsey A Carter, Patricia Vangeneugden, Sofia Weaver, Michael Stout, Michael J Beckstead
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Abstract

Opioid abuse and overdose are major societal issues, and use of opioids among the elderly is increasing at a rapid rate. Despite this increase in opioid use, overdose, and use disorders among the elderly, little is known about abuse potential in a healthy aged population due to technical difficulties with intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (19 weeks) and old (101 weeks) were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. While baseline intake was greater in the old compared to young mice self-administering remifentanil, we did not see an increased intake with age at either dose of fentanyl tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but this was not seen for fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.
老年小鼠静脉注射阿片类药物的自我给药速度更快,但对摄入量的影响各不相同
阿片类药物的滥用和过量是一个重大的社会问题,而老年人使用阿片类药物的人数正在快速增加。尽管老年人使用阿片类药物、用药过量和用药紊乱的情况有所增加,但由于对老年啮齿动物进行静脉自我给药存在技术上的困难,因此人们对健康老年人群滥用阿片类药物的可能性知之甚少。本研究的目的是解决文献中关于老年小鼠和年轻小鼠阿片类药物(瑞芬太尼和芬太尼)自我给药的年龄依赖性差异的重要空白。研究人员将雌雄小鼠分为幼鼠(19周)和老 鼠(101周)两组,每天训练它们自我静脉注射芬太尼或瑞芬太尼。在老龄和幼龄小鼠中,对两种药物的习得、摄入和强迫戒断后的线索反应进行了测量,并绘制了剂量反应曲线(瑞芬太尼)和剂量递增曲线(芬太尼)。老龄小鼠比年轻小鼠更快、更准确地学会了瑞芬太尼和芬太尼的自我给药。虽然与年轻小鼠相比,老年小鼠自我给药瑞芬太尼的基线摄入量更大,但在测试的两种芬太尼剂量下,我们都没有发现摄入量随年龄增长而增加。此外,与年轻小鼠相比,老年小鼠在强迫戒断后对以前与瑞芬太尼相关的线索的反应潜伏期更长,但对芬太尼的反应潜伏期却不长。这些数据共同表明,与年轻小鼠相比,老年群体可能更容易滥用阿片类药物,并强调了今后研究导致这种脆弱性增加的机制的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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