背景:在全球和美国,尼古丁和烟草的使用仍然很高。为巨额医疗支出做出贡献。随着电子烟使用的增加,重要的是要有吸入尼古丁暴露的临床相关模型。这项研究旨在将先前的临床前尼古丁吸入动物数据扩展到女性,并提供行为和血清药代动力学。
方法:我们测试了两种吸入剂量的尼古丁(24mg/ml和59mg/ml),并将其与注射剂量(0.4mg/kg和1mg/kg)进行了比较。此外,我们评估了相同剂量后的运动行为。在给药后10分钟和120分钟时收集血液。我们通过LC-MS/MS评估了尼古丁和可替宁血清浓度。
结果:表明,尽管两种给药途径的高剂量和低剂量给药的尼古丁血清浓度相似,路线对运动行为有不同的影响。吸入的尼古丁显示出运动活性的剂量依赖性降低,而注射剂量则显示出相反的趋势。
结论:我们的结果表明,在建立尼古丁暴露的临床前模型时,给药途径是一个重要因素。鉴于弱势群体中电子烟的总体使用量正在上升,我们的研究提供了重要的行为和药代动力学信息,以促进我们目前对尼古丁蒸气暴露影响的有限理解。
结论:本研究强调了相似剂量尼古丁的不同给药途径之间的行为差异。使用低剂量和高剂量的尼古丁,我们发现不同给药途径的尼古丁血清浓度相似。我们的结果表明,不同的给药途径对运动活动具有相反的影响。这些发现为未来的行为模型提供了重要的启示。
BACKGROUND: Nicotine and tobacco use remain high both globally and in the United States, contributing to large health care expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure.
OBJECTIVE: This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics. We tested two inhalation doses of nicotine (24 mg/mL and 59 mg/ mL) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC-MS/MS.
RESULTS: Showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend.
CONCLUSIONS: Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure.
CONCLUSIONS: This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.