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Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila

Male flies under the influence of ethanol display disinhibited courtship, which is augmented with repeated ethanol exposures. We have previously shown that dopamine is important for this type of ethanol-induced behavioral sensitization but the underlying mechanism is unknown. Here we report that Dop...

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Autores principales: Aranda, Gissel P., Hinojos, Samantha J., Sabandal, Paul R., Evans, Peter D., Han, Kyung-An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539124/
https://www.ncbi.nlm.nih.gov/pubmed/28824387
http://dx.doi.org/10.3389/fnsys.2017.00056
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author Aranda, Gissel P.
Hinojos, Samantha J.
Sabandal, Paul R.
Evans, Peter D.
Han, Kyung-An
author_facet Aranda, Gissel P.
Hinojos, Samantha J.
Sabandal, Paul R.
Evans, Peter D.
Han, Kyung-An
author_sort Aranda, Gissel P.
collection PubMed
description Male flies under the influence of ethanol display disinhibited courtship, which is augmented with repeated ethanol exposures. We have previously shown that dopamine is important for this type of ethanol-induced behavioral sensitization but the underlying mechanism is unknown. Here we report that DopEcR, an insect G-protein coupled receptor that binds to dopamine and steroid hormone ecdysone, is a major receptor mediating courtship sensitization. Upon daily ethanol administration, dumb and damb mutant males defective in D1 (dDA1/DopR1) and D5 (DAMB/DopR2) dopamine receptors, respectively, showed normal courtship sensitization; however, the DopEcR-deficient der males exhibited greatly diminished sensitization. der mutant males nevertheless developed normal tolerance to the sedative effect of ethanol, indicating a selective function of DopEcR in chronic ethanol-associated behavioral plasticity. DopEcR plays a physiological role in behavioral sensitization since courtship sensitization in der males was reinstated when DopEcR expression was induced during adulthood but not during development. When examined for the DopEcR’s functional site, the der mutant’s sensitization phenotype was fully rescued by restored DopEcR expression in the mushroom body (MB) αβ and γ neurons. Consistently, we observed DopEcR immunoreactivity in the MB calyx and lobes in the wild-type Canton-S brain, which was barely detectable in the der brain. Behavioral sensitization to the locomotor-stimulant effect has been serving as a model for ethanol abuse and addiction. This is the first report elucidating the mechanism underlying behavioral sensitization to another stimulant effect of ethanol.
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spelling pubmed-55391242017-08-18 Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila Aranda, Gissel P. Hinojos, Samantha J. Sabandal, Paul R. Evans, Peter D. Han, Kyung-An Front Syst Neurosci Neuroscience Male flies under the influence of ethanol display disinhibited courtship, which is augmented with repeated ethanol exposures. We have previously shown that dopamine is important for this type of ethanol-induced behavioral sensitization but the underlying mechanism is unknown. Here we report that DopEcR, an insect G-protein coupled receptor that binds to dopamine and steroid hormone ecdysone, is a major receptor mediating courtship sensitization. Upon daily ethanol administration, dumb and damb mutant males defective in D1 (dDA1/DopR1) and D5 (DAMB/DopR2) dopamine receptors, respectively, showed normal courtship sensitization; however, the DopEcR-deficient der males exhibited greatly diminished sensitization. der mutant males nevertheless developed normal tolerance to the sedative effect of ethanol, indicating a selective function of DopEcR in chronic ethanol-associated behavioral plasticity. DopEcR plays a physiological role in behavioral sensitization since courtship sensitization in der males was reinstated when DopEcR expression was induced during adulthood but not during development. When examined for the DopEcR’s functional site, the der mutant’s sensitization phenotype was fully rescued by restored DopEcR expression in the mushroom body (MB) αβ and γ neurons. Consistently, we observed DopEcR immunoreactivity in the MB calyx and lobes in the wild-type Canton-S brain, which was barely detectable in the der brain. Behavioral sensitization to the locomotor-stimulant effect has been serving as a model for ethanol abuse and addiction. This is the first report elucidating the mechanism underlying behavioral sensitization to another stimulant effect of ethanol. Frontiers Media S.A. 2017-08-02 /pmc/articles/PMC5539124/ /pubmed/28824387 http://dx.doi.org/10.3389/fnsys.2017.00056 Text en Copyright © 2017 Aranda, Hinojos, Sabandal, Evans and Han. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Aranda, Gissel P.
Hinojos, Samantha J.
Sabandal, Paul R.
Evans, Peter D.
Han, Kyung-An
Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title_full Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title_fullStr Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title_full_unstemmed Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title_short Behavioral Sensitization to the Disinhibition Effect of Ethanol Requires the Dopamine/Ecdysone Receptor in Drosophila
title_sort behavioral sensitization to the disinhibition effect of ethanol requires the dopamine/ecdysone receptor in drosophila
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539124/
https://www.ncbi.nlm.nih.gov/pubmed/28824387
http://dx.doi.org/10.3389/fnsys.2017.00056
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