Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, Baltimore, MD 21224.
eNeuro. 2017 Oct 30;4(5). doi: 10.1523/ENEURO.0323-17.2017. eCollection 2017 Sep-Oct.
While opioid abuse is an established medical and public health issue, the increased availability of highly potent synthetic opioids, such as fentanyl, has given rise to acute health complications, including a comatose state and death during drug overdose. Since respiratory depression that leads to acute hypoxia is the most dangerous complication of opioid drug use, we examined the effects of intravenous heroin and heroin contaminated with 10% fentanyl on oxygen levels in the nucleus accumbens (NAc) monitored using high-speed amperometry in freely moving rats. Additionally, we examined the effects of heroin, fentanyl, and their mixture on locomotion and temperatures in the NAc, temporal muscle, and skin. Both fentanyl and heroin at human-relevant doses (400 and 40 μg/kg, respectively) induced rapid, strong and transient decreases in NAc oxygen, indicative of brain hypoxia. When the heroin-fentanyl mixture was injected, the NAc hypoxic response was greatly potentiated in its duration, suggesting sustained hypoxia. In contrast to modest, monophasic brain temperature increases caused by heroin alone, the heroin-fentanyl mixture induced a biphasic temperature response, with a prominent postinjection decrease resulting from peripheral vasodilation. This hypothermic effect, albeit much smaller and more transient, was typical of fentanyl injected alone. Our findings indicate that accidental use of fentanyl instead of heroin, or even a relatively minor contamination of "street heroin" with fentanyl, poses great danger for acute health complications, including a comatose state and death.
虽然阿片类药物滥用是一个既定的医学和公共卫生问题，但高浓度合成阿片类药物（如芬太尼）的供应增加，导致了严重的健康并发症，包括昏迷状态和药物过量导致的死亡。由于呼吸抑制导致急性缺氧是阿片类药物使用最危险的并发症，我们使用高速安培法在自由活动的大鼠中检查了静脉注射海洛因和含有 10%芬太尼的海洛因对伏隔核（NAc）氧水平的影响。此外，我们还检查了海洛因、芬太尼及其混合物对 NAc 中运动和温度的影响，包括 temporal muscle 和皮肤。芬太尼和海洛因在人体相关剂量（分别为 400 和 40 μg/kg）下均迅速、强烈且短暂地降低了 NAc 中的氧水平，表明存在脑缺氧。当注射海洛因-芬太尼混合物时，NAc 的缺氧反应在持续时间上大大增强，表明持续缺氧。与海洛因单独引起的适度、单相脑温升高相反，海洛因-芬太尼混合物引起双相体温反应，注射后由于外周血管扩张导致体温明显下降。这种降温作用虽然小得多且更短暂，但与单独注射芬太尼的作用典型。我们的研究结果表明，意外使用芬太尼代替海洛因，甚至“街头海洛因”中相对较小的芬太尼污染，都会对急性健康并发症造成极大的危险，包括昏迷状态和死亡。
