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Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster...

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Autores principales: Koyyada, Rajeswari, Latchooman, Nilesh, Jonaitis, Julius, Ayoub, Samir S., Corcoran, Olivia, Casalotti, Stefano O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861182/
https://www.ncbi.nlm.nih.gov/pubmed/29593550
http://dx.doi.org/10.3389/fphys.2018.00175
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author Koyyada, Rajeswari
Latchooman, Nilesh
Jonaitis, Julius
Ayoub, Samir S.
Corcoran, Olivia
Casalotti, Stefano O.
author_facet Koyyada, Rajeswari
Latchooman, Nilesh
Jonaitis, Julius
Ayoub, Samir S.
Corcoran, Olivia
Casalotti, Stefano O.
author_sort Koyyada, Rajeswari
collection PubMed
description Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD.
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spelling pubmed-58611822018-03-28 Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster Koyyada, Rajeswari Latchooman, Nilesh Jonaitis, Julius Ayoub, Samir S. Corcoran, Olivia Casalotti, Stefano O. Front Physiol Physiology Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD. Frontiers Media S.A. 2018-03-14 /pmc/articles/PMC5861182/ /pubmed/29593550 http://dx.doi.org/10.3389/fphys.2018.00175 Text en Copyright © 2018 Koyyada, Latchooman, Jonaitis, Ayoub, Corcoran and Casalotti. 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) and the copyright owner 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 Physiology
Koyyada, Rajeswari
Latchooman, Nilesh
Jonaitis, Julius
Ayoub, Samir S.
Corcoran, Olivia
Casalotti, Stefano O.
Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title_full Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title_fullStr Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title_full_unstemmed Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title_short Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster
title_sort naltrexone reverses ethanol preference and protein kinase c activation in drosophila melanogaster
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861182/
https://www.ncbi.nlm.nih.gov/pubmed/29593550
http://dx.doi.org/10.3389/fphys.2018.00175
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