Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

Abstract Dysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanoga...

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Autores principales:	Mai Kanno, Shun Hiramatsu, Shu Kondo, Hiromu Tanimoto, Toshiharu Ichinose
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54f24ab6548f4efa8c41186895bc82cb
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spelling	oai:doaj.org-article:54f24ab6548f4efa8c41186895bc82cb2021-12-02T12:09:32ZVoluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila10.1038/s41598-021-82813-02045-2322https://doaj.org/article/54f24ab6548f4efa8c41186895bc82cb2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82813-0https://doaj.org/toc/2045-2322Abstract Dysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanogaster offers a unique opportunity to approach this problem with a battery of sophisticated neurogenetic tools available, but how they consume these drugs remains largely unknown. Here, we examined drug self-administration behavior of Drosophila and the underlying neuronal mechanisms. We measured the preference of flies for five different psychoactive substances using a two-choice feeding assay and monitored its long-term changes. We found that flies show acute preference for ethanol and methamphetamine, but not for cocaine, caffeine or morphine. Repeated intake of ethanol, but not methamphetamine, increased over time. Preference for methamphetamine and the long-term escalation of ethanol preference required the dopamine receptor Dop1R1 in the mushroom body. The protein level of Dop1R1 increased after repeated intake of ethanol, but not methamphetamine, which correlates with the acquired preference. Genetic overexpression of Dop1R1 enhanced ethanol preference. These results reveal a striking diversity of response to individual drugs in the fly and the role of dopamine signaling and its plastic changes in controlling voluntary intake of drugs.Mai KannoShun HiramatsuShu KondoHiromu TanimotoToshiharu IchinoseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mai Kanno Shun Hiramatsu Shu Kondo Hiromu Tanimoto Toshiharu Ichinose Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
description	Abstract Dysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanogaster offers a unique opportunity to approach this problem with a battery of sophisticated neurogenetic tools available, but how they consume these drugs remains largely unknown. Here, we examined drug self-administration behavior of Drosophila and the underlying neuronal mechanisms. We measured the preference of flies for five different psychoactive substances using a two-choice feeding assay and monitored its long-term changes. We found that flies show acute preference for ethanol and methamphetamine, but not for cocaine, caffeine or morphine. Repeated intake of ethanol, but not methamphetamine, increased over time. Preference for methamphetamine and the long-term escalation of ethanol preference required the dopamine receptor Dop1R1 in the mushroom body. The protein level of Dop1R1 increased after repeated intake of ethanol, but not methamphetamine, which correlates with the acquired preference. Genetic overexpression of Dop1R1 enhanced ethanol preference. These results reveal a striking diversity of response to individual drugs in the fly and the role of dopamine signaling and its plastic changes in controlling voluntary intake of drugs.
format	article
author	Mai Kanno Shun Hiramatsu Shu Kondo Hiromu Tanimoto Toshiharu Ichinose
author_facet	Mai Kanno Shun Hiramatsu Shu Kondo Hiromu Tanimoto Toshiharu Ichinose
author_sort	Mai Kanno
title	Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
title_short	Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
title_full	Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
title_fullStr	Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
title_full_unstemmed	Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
title_sort	voluntary intake of psychoactive substances is regulated by the dopamine receptor dop1r1 in drosophila
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/54f24ab6548f4efa8c41186895bc82cb
work_keys_str_mv	AT maikanno voluntaryintakeofpsychoactivesubstancesisregulatedbythedopaminereceptordop1r1indrosophila AT shunhiramatsu voluntaryintakeofpsychoactivesubstancesisregulatedbythedopaminereceptordop1r1indrosophila AT shukondo voluntaryintakeofpsychoactivesubstancesisregulatedbythedopaminereceptordop1r1indrosophila AT hiromutanimoto voluntaryintakeofpsychoactivesubstancesisregulatedbythedopaminereceptordop1r1indrosophila AT toshiharuichinose voluntaryintakeofpsychoactivesubstancesisregulatedbythedopaminereceptordop1r1indrosophila
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Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila

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