UC San Diego

This dissertation integrates methods from alcohol and circadian rhythms research to explore relationships between ethanol and circadian rhythms in mice. Ingesting alcohol at certain times of day differentially affects the body; circadian rhythms also impact preference for drinking alcohol at different times of day. The influence of circadian timing on development and maintenance of ethanol drinking patterns was studied in Chapter 2. This showed how establishing a history of ethanol exposure at preferred or non-preferred times of day can influence voluntary ethanol intake for several subsequent weeks. Chapter 3 asked if circadian period is causally related to alcohol intake and investigated this by creating non-24 hour light cycle and measuring ethanol intake in C57BL/6J as well as in high and low alcohol preferring (HAP and LAP) mice. Successful manipulations did not affect amount of ethanol drinking or preference indicating there is not a direct causal effect of circadian period on ethanol intake. Chapter 4 moved from circadian manipulations and voluntary ethanol intake to exploring the influence of chronic ethanol dependence and withdrawal on circadian rhythms. Daily body temperature and activity rhythms were recorded in mice exposed to repeated rounds of ethanol vapor. Ethanol vapor resulted in a reduction in amplitude of the core body temperature rhythm during withdrawal, an effect that was potentiated in subsequent vapor rounds. However, there were no lasting effects observed on body temperature or activity rhythms beyond the first 3 days following ethanol exposure. Together these studies have advanced knowledge about interactions between alcohol and the circadian system. They showed circadian scheduling of ethanol exposure can predict later ethanol intake, having implications that may be beneficial in the development of alcohol use disorder treatments. Experimentally induced changes to circadian period did not predict ethanol intake. This suggests that altering key aspects of the circadian system is not related to amount consumed or preference for ethanol. Finally, changes to circadian rhythms during withdrawal from ethanol signify changes to body function that are related to the degree of prior ethanol exposure; these might be useful in the future as indices of withdrawal or dependence severity.