Abreu-Villaça Yael, Filgueiras Cláudio C, Correa-Santos Monique, Cavina Cristiane C, Naiff Victor F, Krahe Thomas E, Manhães Alex C, Ribeiro-Carvalho Anderson
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil,
Psychopharmacology (Berl). 2015 May;232(10):1693-703. doi: 10.1007/s00213-014-3801-1. Epub 2014 Nov 18.
Thousands of adolescents start smoking daily but information on the effects of tobacco exposure on this age group is scarce. Moreover, the available animal models rely on the effects of nicotine, neglecting other neuroactive components of tobacco.
We investigated the effects of exposure of adolescent mice to tobacco smoke generated from cigarettes containing either high or low levels of nicotine on novelty seeking and anxiety-like behaviors.
From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8 h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74 mg nicotine/cigarette) or 4A1 (LowNic group: 0.14 mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. By the end (PN44-45), shortly (PN49-50), or long after (PN74-75) exposure, mice were tested on the elevated plus maze and on the hole board.
While HighNic mice presented an increased number of head-dips (increased novelty-seeking) and decreased grooming (increased anxiety-like behavior) by the end of adolescent exposure, only the latter effect persisted shortly after its end. Distinctively, LowNic mice presented reduced head-dips both by the end and shortly after exposure as well as decreased grooming shortly and long after the end of exposure. Interestingly, only HighNic mice presented detectable cotinine (nicotine metabolite) serum levels (109.1 ± 24.0 ng/ml).
Our results demonstrate that even adolescent exposure to tobacco smoke with very low nicotine content can have significant short- and long-term behavioral effects, supporting the hypothesis that adolescents can be particularly vulnerable to the effects of cigarette consumption.
每天有成千上万的青少年开始吸烟,但关于烟草暴露对这一年龄段人群影响的信息却很匮乏。此外,现有的动物模型仅依赖尼古丁的作用,而忽略了烟草中的其他神经活性成分。
我们研究了让青春期小鼠暴露于含高或低尼古丁水平香烟所产生的烟草烟雾中,对其新奇寻求行为和焦虑样行为的影响。
从出生后第30天(PN)至45天,将雄性和雌性瑞士小鼠暴露于2R1F(高尼古丁组:每支香烟含1.74毫克尼古丁)或4A1(低尼古丁组:每支香烟含0.14毫克尼古丁)研究用香烟产生的烟草烟雾中(全身暴露,每天8小时,每周7天),而对照小鼠暴露于环境空气中。在暴露结束时(PN44 - 45)、暴露后不久(PN49 - 50)或暴露后很长时间(PN74 - 75),对小鼠进行高架十字迷宫和洞板试验。
在青春期暴露结束时,高尼古丁组小鼠的探洞次数增加(新奇寻求行为增加),理毛行为减少(焦虑样行为增加),但只有后者在暴露结束后不久仍持续存在。不同的是,低尼古丁组小鼠在暴露结束时和结束后不久探洞次数均减少,并且在暴露结束后不久和很长时间理毛行为均减少。有趣的是,只有高尼古丁组小鼠的血清可替宁(尼古丁代谢物)水平可检测到(109.1±24.0纳克/毫升)。
我们的结果表明,即使是青春期暴露于尼古丁含量极低的烟草烟雾中,也会产生显著的短期和长期行为影响,支持了青少年可能对吸烟影响特别敏感的假说。