title: Caffeine promotes wakefulness via dopamine signaling in Drosophila.
abstract: 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.
authors: Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Aleksandra H
authors: AH
authors: Nall
authors: Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Iryna
authors: I
authors: Shakhmantsir
authors: Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
authors: Karol
authors: K
authors: Cichewicz
authors: Genes Circuits Rhythms and Neuropathologies, Brain Plasticity Unit, CNRS, PSL Research University, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France.
authors: Serge
authors: S
authors: Birman
authors: Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
authors: Jay
authors: J
authors: Hirsh
authors: Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.|Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Amita
authors: A
authors: Sehgal
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D002110:Caffeine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine