NICOTINE-INDUCED ACUTE HYPERACTIVITY IS MEDIATED BY DOPAMINERGIC SYSTEM IN A SEXUALLY DIMORPHIC MANNER
NICOTINE-INDUCED ACUTE HYPERACTIVITY IS MEDIATED BY DOPAMINERGIC SYSTEM IN A SEXUALLY DIMORPHIC MANNER
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尼古丁引起的急性多动症是由多巴胺能系统以性二态性方式介导的
DOI：
10.1016/j.neuroscience.2016.06.043
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Li Yan
中科院分区：
文献类型：
--
作者：
Zhang Yunpeng;Guo Jing;Guo Aike;Li Yan
短期接触尼古丁会对小鼠、猴子和人类产生积极影响，包括轻度兴奋、多动症和增强认知能力。然而，这些效应的潜在神经基础和分子机制仍然知之甚少。在这里，使用视频记录系统，我们发现，急性尼古丁给药诱导果蝇的运动过度活动，类似于在更高模式生物中所做的观察。抑制多巴胺能神经元或下调多巴胺1样受体(DOPR)可以消除这种急性尼古丁反应，但令人惊讶的是，只有雄性果蝇才能做到这一点。使用跨突触伙伴的绿色荧光蛋白重组(GFP)方法，我们证明了多巴胺能神经元与大脑广泛区域的乙酰胆碱能神经元具有潜在的突触联系。此外，多巴胺能神经元在尼古丁灌流时被广泛激活，而反应曲线在性别之间存在显著差异。此外，多巴胺能神经元中β1尼古丁乙酰胆碱受体(NAChR)的敲除只在雄性果蝇中取消了急性尼古丁反应，而全神经敲除在两性中都发生了。综上所述，我们的结果表明，在果蝇中，多巴胺能神经元以性别二态的方式介导尼古丁诱导的急性运动多动，而果蝇β1nAChR亚单位在这种尼古丁反应中起着至关重要的作用。这些发现为急性尼古丁效应的分子和神经基础提供了重要的见解，潜在的机制可能在不同物种中发挥保守的作用。
Short-term exposure to nicotine induces positive effects in mice, monkeys and humans, including mild euphoria, hyperactivity, and enhanced cognition. However, the underlying neural basis and molecular mechanisms for these effects remain poorly understood. Here, using a video recording system, we find that acute nicotine administration induces locomotor hyperactivity inDrosophila, similar to observations made in higher model organisms. Suppressing dopaminergic neurons or down-regulating dopamine 1-like receptor (DopR) abolishes this acute nicotine response, but surprisingly, does so only in male flies. Using a GFP reconstitution across synaptic partners (GRASP) approach, we show that dopaminergic neurons possess potential synaptic connections with acetylcholinergic neurons in wide regions of the brain. Furthermore, dopaminergic neurons are widely activated upon nicotine perfusion in both sexes, while the response curve differs significantly between the sexes. Moreover, knockdown of the β1 nicotine acetylcholine receptor (nAChR) in dopaminergic neurons abolishes the acute nicotine response only in male flies, while panneural knock-down occurs in both sexes. Taken together, our results reveal that in fruit flies, dopaminergic neurons mediate nicotine-induced acute locomotor hyperactivity in a sexually dimorphic manner, andDrosophilaβ1 nAChR subunit plays a crucial role in this nicotine response. These findings provide important insights into the molecular and neural basis of acute nicotine effects, and the underlying mechanisms may play conserved roles across species.