Rev-erb α Knockout Reduces Ethanol Consumption and Preference in Male and Female Mice.

Autor: Al-Sabagh, Yasmine, Thorpe, Hayley Hope Allyssa, Jenkins, Bryan William, Hamidullah, Shahnaza, Talhat, Malik Asfandyaar, Suggett, Cara Beth, Reitz, Cristine Joelle, Rasouli, Mina, Martino, Tami Avril, Khokhar, Jibran Younis
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Zdroj: International Journal of Molecular Sciences; May2022, Vol. 23 Issue 9, p5197-5197, 12p
Abstrakt: Alcohol use is a contributor in the premature deaths of approximately 3 million people annually. Among the risk factors for alcohol misuse is circadian rhythm disruption; however, this connection remains poorly understood. Inhibition of the circadian nuclear receptor REV-ERBα is known to disrupt molecular feedback loops integral to daily oscillations, and impact diurnal fluctuations in the expression of proteins required for reward-related neurotransmission. However, the role of REV-ERBα in alcohol and substance use-related phenotypes is unknown. Herein, we used a Rev-erbα knockout mouse line and ethanol two-bottle choice preference testing to show that disruption of Rev-erbα reduces ethanol preference in male and female mice. Rev-erbα null mice showed the lowest ethanol preference in a two-bottle choice test across all genotypes, whereas there were no ethanol preference differences between heterozygotes and wildtypes. In a separate experiment, alcohol-consuming wildtype C57Bl/6N mice were administered the REV-ERBα/β inhibitor SR8278 (25 mg/kg or 50 mg/kg) for 7 days and alcohol preference was evaluated daily. No differences in alcohol preference were observed between the treatment and vehicle groups. Our data provides evidence that genetic variation in REV-ERBα may contribute to differences in alcohol drinking. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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