| First Author | Al-Sabagh Y | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 9 | PubMed ID | 35563586 |
| Mgi Jnum | J:325648 | Mgi Id | MGI:7279876 |
| Doi | 10.3390/ijms23095197 | Citation | Al-Sabagh Y, et al. (2022) Rev-erbalpha Knockout Reduces Ethanol Consumption and Preference in Male and Female Mice. Int J Mol Sci 23(9) |
| abstractText | 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-ERBalpha 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-ERBalpha in alcohol and substance use-related phenotypes is unknown. Herein, we used a Rev-erbalpha knockout mouse line and ethanol two-bottle choice preference testing to show that disruption of Rev-erbalpha reduces ethanol preference in male and female mice. Rev-erbalpha 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-ERBalpha/beta 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-ERBalpha may contribute to differences in alcohol drinking. |
