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

Tytuł:: Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking.
Autorzy:: Kwok C; California State University East Bay, Hayward, CA, USA.; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Lei K; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Pedrozo V; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Anderson L; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Ghotra S; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Walsh M; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Li L; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Yu J; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Hopf FW; Department of Neurology, University of California at San Francisco, San Francisco, CA, USA. .; Department of Psychiatry, Indiana University School of Medicine, 320 W. 15th Street, NB 300E, Indianapolis, IN, 46202, USA. .
Źródło:: Scientific reports [Sci Rep] 2021 Jan 08; Vol. 11 (1), pp. 231. Date of Electronic Publication: 2021 Jan 08.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Binge Drinking/*metabolism
Nucleus Accumbens/*metabolism
Orexin Receptors/*metabolism
Receptors, AMPA/*metabolism
Animals ; Female ; Male ; Mice ; Sex Characteristics
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Grant Information:: P50 AA017072 United States AA NIAAA NIH HHS
Substance Nomenclature:: 0 (Hcrtr1 protein, mouse)
0 (Orexin Receptors)
0 (Receptors, AMPA)
Entry Date(s):: Date Created: 20210109 Date Completed: 20210809 Latest Revision: 20230127
Update Code:: 20240105
PubMed Central ID:: PMC7794293
DOI:: 10.1038/s41598-020-79935-2
PMID:: 33420199
: Czasopismo naukowe

Pełny tekst

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.

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