Caffeine promotes wakefulness via dopamine signaling in Drosophila

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 Drosoph...

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Bibliographic Details
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:
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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
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep20938