Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking

Abstract Alcohol use disorder exhausts substantial social and economic costs, with recent dramatic increases in female problem drinking. Thus, it is critically important to understand signaling differences underlying alcohol consumption across the sexes. Orexin-1 receptors (Ox1Rs) can strongly promo...

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Autores principales:	Claudina Kwok, Kelly Lei, Vincent Pedrozo, Lexy Anderson, Shahbaj Ghotra, Margaret Walsh, Laura Li, JiHwan Yu, Frederic Woodward Hopf
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45f3c45bd17440fbae256198e59902a2
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spelling	oai:doaj.org-article:45f3c45bd17440fbae256198e59902a22021-12-02T11:46:07ZDifferential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking10.1038/s41598-020-79935-22045-2322https://doaj.org/article/45f3c45bd17440fbae256198e59902a22021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79935-2https://doaj.org/toc/2045-2322Abstract Alcohol use disorder exhausts substantial social and economic costs, with recent dramatic increases in female problem drinking. Thus, it is critically important to understand signaling differences underlying alcohol consumption across the sexes. Orexin-1 receptors (Ox1Rs) can strongly promote motivated behavior, and we previously identified Ox1Rs within nucleus accumbens shell (shell) as crucial for driving binge intake in higher-drinking male mice. Here, shell Ox1R inhibition did not alter female mouse alcohol drinking, unlike in males. Also, lower dose systemic Ox1R inhibition reduced compulsion-like alcohol intake in both sexes, indicating that female Ox1Rs can drive some aspects of pathological consumption, and higher doses of systemic Ox1R inhibition (which might have more off-target effects) reduced binge drinking in both sexes. In contrast to shell Ox1Rs, inhibiting shell calcium-permeable AMPA receptors (CP-AMPARs) strongly reduced alcohol drinking in both sexes, which was specific to alcohol since this did not reduce saccharin intake in either sex. Our results together suggest that the shell critically regulates binge drinking in both sexes, with shell CP-AMPARs supporting intake in both sexes, while shell Ox1Rs drove drinking only in males. Our findings provide important new information about sex-specific and -general mechanisms that promote binge alcohol intake and possible targeted therapeutic interventions.Claudina KwokKelly LeiVincent PedrozoLexy AndersonShahbaj GhotraMargaret WalshLaura LiJiHwan YuFrederic Woodward HopfNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudina Kwok Kelly Lei Vincent Pedrozo Lexy Anderson Shahbaj Ghotra Margaret Walsh Laura Li JiHwan Yu Frederic Woodward Hopf Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
description	Abstract Alcohol use disorder exhausts substantial social and economic costs, with recent dramatic increases in female problem drinking. Thus, it is critically important to understand signaling differences underlying alcohol consumption across the sexes. Orexin-1 receptors (Ox1Rs) can strongly promote motivated behavior, and we previously identified Ox1Rs within nucleus accumbens shell (shell) as crucial for driving binge intake in higher-drinking male mice. Here, shell Ox1R inhibition did not alter female mouse alcohol drinking, unlike in males. Also, lower dose systemic Ox1R inhibition reduced compulsion-like alcohol intake in both sexes, indicating that female Ox1Rs can drive some aspects of pathological consumption, and higher doses of systemic Ox1R inhibition (which might have more off-target effects) reduced binge drinking in both sexes. In contrast to shell Ox1Rs, inhibiting shell calcium-permeable AMPA receptors (CP-AMPARs) strongly reduced alcohol drinking in both sexes, which was specific to alcohol since this did not reduce saccharin intake in either sex. Our results together suggest that the shell critically regulates binge drinking in both sexes, with shell CP-AMPARs supporting intake in both sexes, while shell Ox1Rs drove drinking only in males. Our findings provide important new information about sex-specific and -general mechanisms that promote binge alcohol intake and possible targeted therapeutic interventions.
format	article
author	Claudina Kwok Kelly Lei Vincent Pedrozo Lexy Anderson Shahbaj Ghotra Margaret Walsh Laura Li JiHwan Yu Frederic Woodward Hopf
author_facet	Claudina Kwok Kelly Lei Vincent Pedrozo Lexy Anderson Shahbaj Ghotra Margaret Walsh Laura Li JiHwan Yu Frederic Woodward Hopf
author_sort	Claudina Kwok
title	Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
title_short	Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
title_full	Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
title_fullStr	Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
title_full_unstemmed	Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking
title_sort	differential importance of nucleus accumbens ox1rs and ampars for female and male mouse binge alcohol drinking
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/45f3c45bd17440fbae256198e59902a2
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Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking

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