Drosophila D1 dopamine receptor mediates caffeine-induced arousal

The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)-induced wakefulness remain unexplored. Here,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (51), p.20392-20397
Main Authors: Andretic, Rozi, Kim, Young-Cho, Jones, Frederick S, Han, Kyung-An, Greenspan, Ralph J
Format: Article
Language:English
Subjects:
Adenosine - metabolism
Animals
Arousal - drug effects
Behavioral neuroscience
Biological Sciences
brain
Caffeine
Caffeine - pharmacology
caffeine induced wakefulness
dopamine
Dopamine - metabolism
dopaminergic transmission
Down regulation
Down-Regulation - genetics
Drosophila
Drosophila melanogaster
Drosophila Proteins - genetics
Drosophila Proteins - physiology
Gene expression
insect behavior
Insects
Mammals
Methamphetamine
Methamphetamine - pharmacology
Mushroom bodies
Mutation
Neurons
neurophysiology
Neurotransmitter Agents
Organisms, Genetically Modified
Proteins
Purinergic P1 receptors
Receptors
Receptors, Dopamine - genetics
Receptors, Dopamine - physiology
Sleep
Transgenic animals
Wakefulness
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Summary:The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)-induced wakefulness remain unexplored. Here, we show that in Drosophila, as in mammals, the wake-promoting effect of CAFF involves both the adenosinergic and dopaminergic systems. By measuring behavioral responses in mutant and transgenic flies exposed to different drug-feeding regimens, we show that CAFF-induced wakefulness requires the Drosophila D1 dopamine receptor (dDA1) in the mushroom bodies. In WT flies, CAFF exposure leads to downregulation of dDA1 expression, whereas the transgenic overexpression of dDA1 leads to CAFF resistance. The wake-promoting effects of methamphetamine require a functional dopamine transporter as well as the dDA1, and they engage brain areas in addition to the mushroom bodies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0806776105