Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats
Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats
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DOI：
10.1007/s00213-007-0876-y
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Leslie, Frances M.
中科院分区：
文献类型：
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作者：
Franke, Ryan M.;Belluzzi, James D.;Leslie, Frances M.
许多孕妇继续吸烟，尽管母亲吸烟与后代的神经行为缺陷有很强的联系。虽然啮齿动物妊娠期尼古丁（GN）治疗被用作母体吸烟的主要动物模型，但烟草烟雾含有超过4000种成分，包括单胺氧化酶抑制剂（MAOIs）。目的本研究的目的是确定妊娠期暴露于尼古丁和MAOIs对青春期大鼠可卡因诱导的运动致敏的影响之间是否存在相互作用。材料和方法孕鼠在妊娠第4天植入渗透性微型泵，分别给药生理盐水、尼古丁（3 mg/kg /d）、MAOIs氯代碱和去戊烯醇（分别为1和0.25 mg/kg /d）或尼古丁/氯代碱/去戊烯醇（GMN）。对青春期雌性后代进行可卡因诱导的运动致敏试验。从出生后(P)第32-36天开始，每天给予生理盐水或可卡因（5或15 mg/kg，腹腔注射），并在第51天（第20天）给予可卡因（15 mg/kg）。结果可卡因的慢性效应组间存在差异，但急性效应组间无差异。妊娠期MAOI治疗，无论有无尼古丁，在第5天增加了对可卡因的动态反应，而在垂直活动方面则相反。在可卡因刺激日观察到不同的适应性反应。在第20天的可卡因挑战前，GNM动物在可卡因相关环境中表现出增强的运动活动。相比之下，只有GN动物对可卡因刺激表现出显著的运动敏化。结论妊娠期尼古丁和MAOIs均影响大脑发育。这种相互作用可能使青少年对药物滥用敏感，应在母亲吸烟的动物模型中加以考虑。
Rationale Many pregnant women continue to smoke, despite a strong association between maternal smoking and neurobehavioral deficits in the offspring. Although gestational nicotine (GN) treatment in rodents is used as the primary animal model of maternal smoking, tobacco smoke contains more than 4,000 constituents, including monoamine oxidase inhibitors (MAOIs).Objectives The aim of this study was to determine whether there are interactions between the effects of gestational exposure to nicotine and MAOIs on cocaine-induced locomotor sensitization in adolescent rats.Materials and methods Pregnant rats were implanted on day 4 of gestation with osmotic minipumps delivering saline, nicotine (3 mg/kg per day), the MAOIs clorgyline and deprenyl (1 and 0.25 mg/kg per day, respectively), or nicotine/clorgyline/deprenyl (GMN). Adolescent female offspring were tested for cocaine-induced locomotor sensitization. Animals were treated with saline or cocaine (5 or 15 mg/kg, intraperitoneally) daily from postnatal (P) days 32-36 and challenged with cocaine (15 mg/kg) on P51 (day 20).Results Group differences were observed in chronic but not acute effects of cocaine. Whereas gestational MAOI treatment, with or without nicotine, increased ambulatory response to cocaine on day 5, the opposite was found for vertical activity. Different adaptive responses were observed on cocaine challenge day. GNM animals exhibited enhanced locomotor activity in the cocaine-associated environment before cocaine challenge on day 20. In contrast, only GN animals exhibited significant locomotor sensitization to the cocaine challenge.Conclusions Gestational nicotine and MAOIs both influence brain development. Such interactions may sensitize adolescents to drug abuse and should be considered in animal models of maternal smoking.