The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice

Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In thi...

Full description

Bibliographic Details
Main Authors: Abanoub Aziz Rizk, Bryan W. Jenkins, Yasmine Al-Sabagh, Shahnaza Hamidullah, Cristine J. Reitz, Mina Rasouli, Tami A. Martino, Jibran Y. Khokhar
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/4/701
_version_ 1797434647475388416
author Abanoub Aziz Rizk
Bryan W. Jenkins
Yasmine Al-Sabagh
Shahnaza Hamidullah
Cristine J. Reitz
Mina Rasouli
Tami A. Martino
Jibran Y. Khokhar
author_facet Abanoub Aziz Rizk
Bryan W. Jenkins
Yasmine Al-Sabagh
Shahnaza Hamidullah
Cristine J. Reitz
Mina Rasouli
Tami A. Martino
Jibran Y. Khokhar
author_sort Abanoub Aziz Rizk
collection DOAJ
description Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., Clock<sup>Δ19/Δ19</sup> mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male Clock<sup>Δ19/Δ19</sup> mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, Clock<sup>Δ19/Δ19</sup> mice displayed increased alcohol consumption and preference. Sex differences were not apparent in Clock<sup>Δ19/Δ19</sup> mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the <i>Clock</i> gene greatly increases alcohol consumption and abolishes sex differences present in WT animals.
first_indexed 2024-03-09T10:35:11Z
format Article
id doaj.art-7e1724a336bb44a18302e4c646f19555
institution Directory Open Access Journal
issn 2073-4425
language English
last_indexed 2024-03-09T10:35:11Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series Genes
spelling doaj.art-7e1724a336bb44a18302e4c646f195552023-12-01T20:57:37ZengMDPI AGGenes2073-44252022-04-0113470110.3390/genes13040701The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in MiceAbanoub Aziz Rizk0Bryan W. Jenkins1Yasmine Al-Sabagh2Shahnaza Hamidullah3Cristine J. Reitz4Mina Rasouli5Tami A. Martino6Jibran Y. Khokhar7Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaShift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., Clock<sup>Δ19/Δ19</sup> mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male Clock<sup>Δ19/Δ19</sup> mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, Clock<sup>Δ19/Δ19</sup> mice displayed increased alcohol consumption and preference. Sex differences were not apparent in Clock<sup>Δ19/Δ19</sup> mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the <i>Clock</i> gene greatly increases alcohol consumption and abolishes sex differences present in WT animals.https://www.mdpi.com/2073-4425/13/4/701shiftworksex differencesalcohol use disorderchronobiologychronicity
spellingShingle Abanoub Aziz Rizk
Bryan W. Jenkins
Yasmine Al-Sabagh
Shahnaza Hamidullah
Cristine J. Reitz
Mina Rasouli
Tami A. Martino
Jibran Y. Khokhar
The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
Genes
shiftwork
sex differences
alcohol use disorder
chronobiology
chronicity
title The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
title_full The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
title_fullStr The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
title_full_unstemmed The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
title_short The Impact of Sex, Circadian Disruption, and the Clock<sup>Δ19/Δ19</sup> Genotype on Alcohol Drinking in Mice
title_sort impact of sex circadian disruption and the clock sup δ19 δ19 sup genotype on alcohol drinking in mice
topic shiftwork
sex differences
alcohol use disorder
chronobiology
chronicity
url https://www.mdpi.com/2073-4425/13/4/701
work_keys_str_mv AT abanoubazizrizk theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT bryanwjenkins theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT yasminealsabagh theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT shahnazahamidullah theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT cristinejreitz theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT minarasouli theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT tamiamartino theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT jibranykhokhar theimpactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT abanoubazizrizk impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT bryanwjenkins impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT yasminealsabagh impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT shahnazahamidullah impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT cristinejreitz impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT minarasouli impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT tamiamartino impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice
AT jibranykhokhar impactofsexcircadiandisruptionandtheclocksupd19d19supgenotypeonalcoholdrinkinginmice