Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans.
Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans.
复制标题
开发脉冲静脉尼古丁输注作为人类吸入尼古丁的模型。
DOI：
10.1007/s00213-022-06162-0
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发表时间：
2022
影响因子：
3.4
通讯作者：
Sofuoglu,Mehmet
中科院分区：
文献类型：
--
作者：
DeAquino,JoaoP;DeVito,EliseE;Xie,Catherine;Meyerovich,Julia;Parida,Suprit;Gueorguieva,Ralitza;Sofuoglu,Mehmet
理由：虽然香烟中的尼古丁以喷雾剂的形式释放，但大多数临床前和人体静脉注射尼古丁的研究都使用了丸剂或连续输注。目的探讨建立吸烟者脉冲尼古丁输注模型的可行性。方法12名成年吸烟者在一夜戒烟后进行了5次实验。采用交叉设计，在每个疗程中，参与者被分配到5种条件中的1种：(1)高/快：在5次脉冲输注中提供1.0 mg尼古丁，然后15次生理盐水输注；(2)高/慢：1.0 mg尼古丁通过20次脉冲输注；(3)低/快：5次脉冲输注0.2 mg尼古丁，然后15次生理盐水输注；(4)低/慢：20次脉冲输注0.2 mg尼古丁；(5)安慰剂：20次脉冲输注生理盐水。主观药物效应、吸烟冲动、尼古丁戒断和认知表现在每个疗程中都被测量。结果高/快和高/慢两种情况下，“头急”和“兴奋”程度均较高（p< 0.05）。高/快条件对吸烟冲动和尼古丁戒断的抑制作用也更大（p< 0.05），分别由吸烟冲动问卷和明尼苏达尼古丁戒断量表衡量。与生理盐水相比，高/快和高/慢条件下的心率增加更大（p< 0.01）。最后，连续性能测试表明，给药条件对认知性能没有主要影响。结论这些发现证明了脉冲尼古丁输注模拟吸烟尼古丁传递的可行性。这个模型可以为未来的研究提供信息，测试新的戒烟疗法和烟草监管研究，测试尼古丁减少方法的影响。
RationaleAlthough nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions.ObjectivesTo determine the feasibility of a pulsed-nicotine infusion model in smokers.MethodsFollowing overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1)high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2)high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3)low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4)low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5)placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session.ResultsBoth thehigh/fastandhigh/slowconditions were associated with greater “head rush” and “high” (p< 0.05). Thehigh/fastcondition also provided greater suppression of urges to smoke and nicotine withdrawal (p< 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. Thehigh/fastandhigh/slowconditions produced greater increases in heart rate (p< 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test.ConclusionsThese findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.