TY - JOUR
T1 - Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression
AU - Grigsby, Kolter
AU - Ledford, Courtney
AU - Batish, Tanvi
AU - Kanadibhotla, Snigdha
AU - Smith, Delaney
AU - Firsick, Evan
AU - Tran, Alexander
AU - Townsley, Kayla
AU - Reyes, Kaylee Abril Vasquez
AU - LeBlanc, Katherine
AU - Ozburn, Angela
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - alcohol
KW - circadian
KW - gene expression
KW - nucleus accumbens
KW - suprachiasmatic nucleus
KW - ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=85139800060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139800060&partnerID=8YFLogxK
U2 - 10.3390/ijms231911084
DO - 10.3390/ijms231911084
M3 - Article
C2 - 36232380
AN - SCOPUS:85139800060
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 11084
ER -