The purpose of this study was to investigate how nicotine in the context of water pipe tobacco smoking (WTS) affects depression and anxiety-like behaviors associated with chronic social defeat stress (CSDS). Male C57BL/6 J mice were exposed to WTS or received intraperitoneal injections of nicotine for thirty days then subjected to CSDS for ten days. During CSDS, mice were exposed to WTS or received nicotine injections. The social interaction and open-field tests were used to classify animals as resilient or susceptible to stress and to evaluate their anxiety-like behavior. After behavioral testing, mice continued to be exposed to WTS/nicotine for ten days and their behavior was reexamined. The involvement of brain derived neurotrophic factor signaling in the nicotine-mediated effects was assessed with the tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We found that WTS promotes resilience to stress and rescues social avoidance. Even though WTS initially decreased anxiety-like behaviors, prolonged exposure after the completion of CSDS significantly induced anxiety-like behaviors. Finally, we showed that nicotine mediates the effects of WTS only on resilience to stress by increasing BDNF and TRKB levels and signaling. Our results suggest that the pathways mediating resilience to stress and anxiety are distinct and that nicotine mediates the effects of WTS on social behavior, but not anxiety, by activating BDNF signaling. Significance statement: This study reports the positive effect of WTS and nicotine on social behavior. Furthermore, it shows the negative effects of prolonged WTS on anxiety-like behaviors and suggests that these effects are not necessarily mediated by nicotine. Finally, it identifies BDNF/TRKB signaling pathway as a major mediator of the positive effects of nicotine on social interaction. As a result, this work emphasizes the importance of considering the activation status of this signaling pathway when developing smoking cessation strategies.

中文翻译：

---

尼古丁通过激活BDNF信号传导，在水烟烟草暴露的小鼠模型中诱导对慢性社交衰竭压力的适应力。

这项研究的目的是调查烟斗吸烟（WTS）中的尼古丁如何影响与慢性社交失败压力（CSDS）相关的抑郁和焦虑样行为。将雄性C57BL / 6 J小鼠暴露于WTS或腹膜内注射烟碱30天，然后进行CSDS 10天。在CSDS期间，将小鼠暴露于WTS或接受尼古丁注射。使用社交互动和开放式测试将动物归类为有弹性或易受压力的动物，并评估其焦虑样行为。进行行为测试后，小鼠继续暴露于WTS /烟碱10天，并对其行为进行了重新检查。用原肌球蛋白受体激酶B（TRKB）抑制剂ANA-12评估了脑源性神经营养因子信号传导对尼古丁介导的作用的影响。我们发现，WTS可以增强抵御压力的能力并挽救社会回避。即使WTS最初减轻了焦虑样行为，但CSDS完成后的长时间暴露仍显着诱发了焦虑样行为。最后，我们表明尼古丁通过增加BDNF和TRKB的水平和信号传导，仅介导WTS对抗逆性的作用。我们的结果表明，介导对压力和焦虑的适应力的途径是截然不同的，尼古丁通过激活BDNF信号传导介导WTS对社会行为的影响，而不是焦虑。重要声明：这项研究报告了WTS和尼古丁对社会行为的积极影响。此外，它显示了延长的WTS对焦虑样行为的负面影响，并表明这些影响不一定由尼古丁介导。最后，它确定了BDNF / TRKB信号通路是尼古丁对社会互动产生积极影响的主要媒介。结果，这项工作强调了在制定戒烟策略时考虑该信号通路的激活状态的重要性。