International Journal of Molecular Sciences (May 2022)

<em>Rev-erb</em>α Knockout Reduces Ethanol Consumption and Preference in Male and Female Mice

  • Yasmine Al-Sabagh,
  • Hayley Hope Allyssa Thorpe,
  • Bryan William Jenkins,
  • Shahnaza Hamidullah,
  • Malik Asfandyaar Talhat,
  • Cara Beth Suggett,
  • Cristine Joelle Reitz,
  • Mina Rasouli,
  • Tami Avril Martino,
  • Jibran Younis Khokhar

Journal volume & issue
Vol. 23, no. 9
p. 5197


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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.