Biological psychiatry global open science · 2024
Corticotropin-Releasing Factor Modulates Binge-Like Ethanol Drinking in a Sex-Dependent Manner: Impact of Amygdala Deletion and Inhibition of a Central Amygdala to Lateral Hypothalamus Circuit.
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Bendrath Sophie C, Méndez Hernán G, Dankert Anne M, Lerma-Cabrera Jose Manuel, Carvajal Francisca, Dornellas Ana Paula S, Lee Sophia, Neira Sofia, Haun Harold, Delpire Eric, Navarro Montserrat, Kash Thomas L, Thiele Todd E
Аннотация
BACKGROUND: Binge alcohol drinking is a dangerous behavior that can contribute to the development of more severe alcohol use disorder. Importantly, the rate and severity of alcohol use disorder has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin-releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in CRF systems.
METHODS: In the current report, we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice.
RESULTS: Using chemogenetic tools, we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male but not female mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF1 receptor in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF2 receptor activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking reduced C rf messenger RNA levels in the CeA regardless of sex.
CONCLUSIONS: These observations provide novel evidence that CRF+ CeA to LH neurocircuitry is more sensitive for modulating binge-like ethanol intake in male mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.
METHODS: In the current report, we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice.
RESULTS: Using chemogenetic tools, we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male but not female mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF1 receptor in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF2 receptor activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking reduced C rf messenger RNA levels in the CeA regardless of sex.
CONCLUSIONS: These observations provide novel evidence that CRF+ CeA to LH neurocircuitry is more sensitive for modulating binge-like ethanol intake in male mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.