Cocaine and amphetamine regulated transcript (CART) mediates sex differences in binge drinking through central taste circuits

The neuropeptide cocaine- and amphetamine-regulated transcript (CART) has been implicated in alcohol consumption and reward behaviours, yet mechanisms mediating these effects have yet to be identified. Using a transgenic CART knockout (KO) mouse line we uncovered a sexually dimorphic effect of CART...

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Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2024-02, Vol.49 (3), p.541-550
Main Authors: Maddern, Xavier J, Letherby, Bethany, Ch'ng, Sarah S, Pearl, Amy, Gogos, Andrea, Lawrence, Andrew J, Walker, Leigh C
Format: Article
Language:English
Subjects:
Alcohol
Alcohol use
Alcoholism
Amphetamines
Amygdala
Animals
Binge Drinking - genetics
Cocaine
Cocaine - pharmacology
Cocaine- and amphetamine-regulated transcript protein
Drinking behavior
Ethanol
Female
Females
Male
Mice
Nerve Tissue Proteins - genetics
Sex Characteristics
Sex differences
Sex hormones
Sexual dimorphism
Taste
Transgenic mice
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Summary:The neuropeptide cocaine- and amphetamine-regulated transcript (CART) has been implicated in alcohol consumption and reward behaviours, yet mechanisms mediating these effects have yet to be identified. Using a transgenic CART knockout (KO) mouse line we uncovered a sexually dimorphic effect of CART in binge drinking, with male CART KO mice increasing intake, whilst female CART KO mice decreased their alcohol intake compared to controls. Female CART KO mice show greater sensitivity to bitter solutions that can be overshadowed through addition of a sweetener, implicating taste as a factor. Further we identify that this is not driven through peripherally circulating sex hormones, but the central nucleus of the amygdala (CeA) is a locus where CART contributes to the regulation of alcohol consumption, with CeA CART neutralisation specifically reducing plain alcohol, but not sweetened alcohol consumption in female mice. These findings may have implications for the development of sex-specific treatment options for alcohol use disorders through targeting the CART system.
ISSN:0893-133X
1740-634X
DOI:10.1038/s41386-023-01712-2