Repeated nicotine vapor inhalation induces behavioral sensitization in male and female C57BL/6 mice
Repeated nicotine vapor inhalation induces behavioral sensitization in male and female C57BL/6 mice
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DOI：
10.1097/fbp.0000000000000562
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发表时间：
2020-09-01
影响因子：
1.6
通讯作者：
Hillhouse, Todd M.
中科院分区：
文献类型：
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作者：
Honeycutt, Sarah C.;Garrett, Patrick I.;Hillhouse, Todd M.
电子烟的使用在过去十年中显著增加。然而，在啮齿动物中尼古丁蒸汽吸入的行为和滥用相关影响的临床前研究有限。本研究使用尼古丁行为致敏模型评价了重复尼古丁蒸汽吸入对雄性和雌性小鼠的影响。对雄性和雌性C57 BL/6小鼠给予汽化尼古丁（0-10.0 mg/ml）或腹膜内给予尼古丁（0.5 mg/kg）的阳性对照，每日一次，持续5天，并评估自发活动。在尼古丁蒸汽吸入之前和之后测量体温以评估体温过低。尼古丁蒸汽吸入（1.0-3.0 mg/ml）产生剂量依赖性行为敏化效应，并在雄性和雌性小鼠中产生体温降低。尼古丁（0.5 mg/kg）也产生了显着的行为敏化。两种给药途径的尼古丁行为致敏作用均未发现性别差异。用非选择性烟碱拮抗剂美加明预处理阻断了由1.0 mg/ml尼古丁蒸汽吸入产生的行为敏化。这些结果表明，尼古丁蒸汽吸入产生的行为敏化呈倒U形曲线，这与注射尼古丁在几种行为模型中的作用相似。此外，用美加明预处理表明，烟碱受体激活是尼古丁蒸汽吸入产生的行为敏化的原因，而不是对蒸汽的条件反应。本研究中使用的方法提供了用于评估重复尼古丁蒸汽吸入的行为影响的额外行为方法，其允许操纵若干变量，包括电子烟液油混合物、电子烟液风味剂、抽吸持续时间等。
Electronic cigarette use has significantly increased over the past decade. However, there is limited preclinical research on the behavioral and abuse-related effects of nicotine vapor inhalation in rodents. The present study evaluates the effects of repeated nicotine vapor inhalation in male and female mice using a nicotine behavioral sensitization model. Male and female C57BL/6 mice were administered vaporized nicotine (0-10.0 mg/ml) or the positive control of intraperitoneally administered nicotine (0.5 mg/kg) once daily for 5 days, and locomotor activity was assessed. Body temperatures were measured before and after nicotine vapor inhalation to assess hypothermia. Nicotine vapor inhalation (1.0-3.0 mg/ml) produced a dose-dependent behavioral sensitization effect and produced hypothermia in male and female mice. Nicotine (0.5 mg/kg) also produced significant behavioral sensitization. No sex differences were found for nicotine behavioral sensitization with either route of administration. Pretreatment with the nonselective nicotinic antagonist mecamylamine blocked the behavioral sensitization produced by 1.0 mg/ml of nicotine vapor inhalation. These results established that nicotine vapor inhalation produces behavioral sensitization in an inverted U-shaped curve that is similar to the effects of injected nicotine across several behavioral models. Additionally, pretreatment with mecamylamine demonstrated that nicotinic receptor activation was responsible for the behavioral sensitization produced by nicotine vapor inhalation and was not a conditioned response to the vapor. The methods used in the present study provide an additional behavioral approach for evaluating the behavioral effects of repeated nicotine vapor inhalation that allows the manipulation of several variables, including e-liquid oil blend, e-liquid flavors, puff duration, etc.