Caffeine promotes wakefulness via dopamine signaling in Drosophila

• Published in: Scientific reports 2016-02, Vol.6 (1), p.20938-20938, Article 20938
• Main Authors: Nall, Aleksandra H., Shakhmantsir, Iryna, Cichewicz, Karol, Birman, Serge, Hirsh, Jay, Sehgal, Amita
• Format: Article
• Language: English
• Subjects: 14; 631/378/2583; 631/378/3920; 64; 64/24; Adenosine; Adenosine receptors; Animals; Arousal; Behavior, Animal - drug effects; Caffeine; Caffeine - pharmacology; Diurnal; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Drosophila melanogaster - drug effects; Drosophila melanogaster - metabolism; Humanities and Social Sciences; Insects; multidisciplinary; Neurons; Nighttime; Psychotropic drugs; Science; Signal Transduction - drug effects; Sleep; Sleep and wakefulness; Synapses - drug effects; Synapses - metabolism; Tyrosine 3-Monooxygenase - metabolism; Wakefulness - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20938

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.