Smith Mark A, Spera Anthony G, Thomas Emma M, Biancorosso Samantha L, Carlson Hannah N
Department of Psychology and Program in Neuroscience, Davidson College, Davidson, NC, USA.
Department of Psychology and Program in Neuroscience, Davidson College, Davidson, NC, USA.
Drug Alcohol Depend. 2025 Jul 19;275:112799. doi: 10.1016/j.drugalcdep.2025.112799.
Xylazine-adulterated fentanyl (i.e., "tranq-dope") has been identified as a national public health threat in the United States. Despite the increasing prevalence of this drug combination, little is known about the interactions between fentanyl and xylazine on measures directly relevant to their addiction liability. The primary objective of this study was to determine whether xylazine enhances or prolongs the mu-opioid mediated discriminative stimulus effects of fentanyl. To this end, male and female Long-Evans rats were trained to discriminate the prototypical mu-opioid agonist, morphine, from saline, and substitution tests were conducted with fentanyl, xylazine, and fentanyl-xylazine combinations. Fentanyl substituted fully for the morphine training stimulus, whereas xylazine failed to substitute fully for the morphine stimulus up to doses that significantly decreased responding. In drug combination tests, xylazine did not influence the acute effects of fentanyl; however, xylazine dose-dependently increased the duration of fentanyl's stimulus effects. These data indicate that xylazine does not produce discriminative stimulus effects like prototypical mu-opioid agonists but prolongs the mu-opioid mediated discriminative stimulus effects of fentanyl, which may partially explain its use in some populations who misuse opioids.
在美国，掺有赛拉嗪的芬太尼（即“tranq-dope”）已被认定为一种全国性公共卫生威胁。尽管这种药物组合的使用日益普遍，但对于芬太尼和赛拉嗪在与其成瘾性直接相关的指标上的相互作用，人们知之甚少。本研究的主要目的是确定赛拉嗪是否会增强或延长芬太尼介导的μ-阿片受体辨别刺激效应。为此，对雄性和雌性朗-埃文斯大鼠进行训练，使其能够区分典型的μ-阿片受体激动剂吗啡和生理盐水，并使用芬太尼、赛拉嗪以及芬太尼-赛拉嗪组合进行替代试验。芬太尼能完全替代吗啡训练刺激，而赛拉嗪在剂量显著降低反应之前，未能完全替代吗啡刺激。在药物联合试验中，赛拉嗪不影响芬太尼的急性效应；然而，赛拉嗪剂量依赖性地增加了芬太尼刺激效应的持续时间。这些数据表明，赛拉嗪不会产生像典型μ-阿片受体激动剂那样的辨别刺激效应，但会延长芬太尼介导的μ-阿片受体辨别刺激效应，这可能部分解释了它在一些滥用阿片类药物人群中的使用情况。
