Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.

Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala i...

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Autores principales:	Heidi M B Lesscher, Julia M Houthuijzen, Marian J Groot Koerkamp, Frank C P Holstege, Louk J M J Vanderschuren
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4aece733fef4eb0aa34fb0f6b1be213
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spelling	oai:doaj.org-article:d4aece733fef4eb0aa34fb0f6b1be2132021-11-18T07:17:46ZAmygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.1932-620310.1371/journal.pone.0037999https://doaj.org/article/d4aece733fef4eb0aa34fb0f6b1be2132012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22629472/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use.Heidi M B LesscherJulia M HouthuijzenMarian J Groot KoerkampFrank C P HolstegeLouk J M J VanderschurenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37999 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heidi M B Lesscher Julia M Houthuijzen Marian J Groot Koerkamp Frank C P Holstege Louk J M J Vanderschuren Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
description	Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use.
format	article
author	Heidi M B Lesscher Julia M Houthuijzen Marian J Groot Koerkamp Frank C P Holstege Louk J M J Vanderschuren
author_facet	Heidi M B Lesscher Julia M Houthuijzen Marian J Groot Koerkamp Frank C P Holstege Louk J M J Vanderschuren
author_sort	Heidi M B Lesscher
title	Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
title_short	Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
title_full	Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
title_fullStr	Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
title_full_unstemmed	Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
title_sort	amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d4aece733fef4eb0aa34fb0f6b1be213
work_keys_str_mv	AT heidimblesscher amygdala1433zasanovelmodulatorofescalatingalcoholintakeinmice AT juliamhouthuijzen amygdala1433zasanovelmodulatorofescalatingalcoholintakeinmice AT marianjgrootkoerkamp amygdala1433zasanovelmodulatorofescalatingalcoholintakeinmice AT frankcpholstege amygdala1433zasanovelmodulatorofescalatingalcoholintakeinmice AT loukjmjvanderschuren amygdala1433zasanovelmodulatorofescalatingalcoholintakeinmice
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Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.

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