Caffeine promotes wakefulness via dopamine signaling in Drosophila.
Caffeine promotes wakefulness via dopamine signaling in Drosophila.
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DOI：
10.1038/srep20938
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发表时间：
2016-02-12
影响因子：
4.6
通讯作者：
Sehgal A
中科院分区：
文献类型：
--
作者：
Nall AH;Shakhmantsir I;Cichewicz K;Birman S;Hirsh J;Sehgal A
咖啡因是世界上消费最广泛的精神药物，但我们对咖啡因如何影响大脑的理解相对不完整。大多数研究集中在咖啡因对腺苷受体的影响上，但也有其他更复杂机制的证据。在果蝇Drosophila melanogaster中，它显示出一种强大的昼夜睡眠/觉醒活动模式，咖啡因独立于一种已知的腺苷受体减少夜间睡眠行为。在这里，我们表明多巴胺是咖啡因在果蝇中的促醒作用所必需的，咖啡因可能在突触前起作用以增加多巴胺信号。我们确定了一组神经元，成对的前内侧（PAM）簇多巴胺能神经元，作为相关的咖啡因反应。PAM神经元在给予咖啡因后显示出增加的活性，并且在激活时促进觉醒。此外，这些神经元的抑制消除了咖啡因对睡眠的抑制。虽然以前的研究主要集中在腺苷受体介导的机制，咖啡因的行动，我们已经确定了多巴胺能神经元的唤醒促进作用的咖啡因。
Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine.