Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression

Abstract

Previous studies (1) support a role of circadian genes in regulating alcohol intake, and (2) reveal that harmful alcohol use alters circadian rhythms. However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol’s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns.

Circadian and seasonal changes in the expression of clock genes in the ovine pars tuberalis

“…It should be mentioned that published evidence indicates that diurnal rhythms in the expression of clock genes may differ within the same species, and could be affected by the analysed tissue and/or genetic differences. A study in high drinking in the dark-1 (HDID-1) mice (Grigsby et al, 2022), which revealed distinct diurnal circadian gene expression patterns in various brain regions, including the SCN, ventral tegmental area, and nucleus accumbens. These patterns diverged not only from each other but also from previous studies on mice, such as the work of Zhang et al (2014).…”