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Ethanol Disruption of the Mammalian Circadian Timing System

Ruby, Christina L.

Abstract Details

2010, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
It is well established that alcohol (ethanol) abuse and dependence are associated with marked disturbances in circadian rhythmicity. Likewise, chronodisruption arising from shift work, sleep disorders, or dysfunction in clock genes that underlie cellular timekeeping may predispose individuals to develop alcoholism. Despite the large body of literature supporting a key link between systems governing circadian timing and those involved in alcohol abuse, very little is known about how ethanol interacts with the mammalian circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This clock is primarily regulated by light, or photic input, which is communicated to the SCN via release of the excitatory neurotransmitter, glutamate, directly from the retina. Other environmental and behavioral information, such as food availability, social interactions, and exercise, also play an essential role in determining clock phase. These nonphotic stimuli are largely mediated by serotonin release in the SCN from the median raphe nucleus. As ethanol perturbs both glutamatergic and serotonergic neurotransmission, these inputs represent potential targets of ethanol in the SCN clock. The experiments in this dissertation were designed to investigate the interactions between ethanol exposure and withdrawal on the photic and nonphotic regulation of circadian behavioral rhythms in rodent models of alcoholism. Microdialysis characterizations of ethanol pharmacokinetics in the SCN and periphery confirmed that physiologically relevant levels of ethanol were present in the SCN after both experimenter and self-administration of the drug, and that a distinct circadian rhythm in central ethanol occurred during chronic drinking. Ethanol and withdrawal impaired photic and nonphotic regulation of general circadian locomotor behavior in hamsters and mice. The specific pattern of disruption was dependent upon species (hamsters versus mice), ethanol dose, and chronicity of ethanol exposure and withdrawal. Mice lacking the clock gene Period 2 continued to display high ethanol intake despite a photocycle challenge mimicking shift work. These results indicate that limiting the time of day ethanol is consumed, bright light exposure, well-timed exercise, and certain pharmaceuticals may minimize the adverse effects of ethanol on circadian rhythms and decrease the drive to drink.
J. David Glass, PhD (Advisor)
Eric Mintz, PhD (Committee Member)
Jennifer Marcinkiewicz, PhD (Committee Member)
Mark Simmons, PhD (Committee Member)
Douglas Delahanty, PhD (Committee Member)
185 p.

Recommended Citations

Citations

  • Ruby, C. L. (2010). Ethanol Disruption of the Mammalian Circadian Timing System [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1270053064

    APA Style (7th edition)

  • Ruby, Christina. Ethanol Disruption of the Mammalian Circadian Timing System. 2010. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1270053064.

    MLA Style (8th edition)

  • Ruby, Christina. "Ethanol Disruption of the Mammalian Circadian Timing System." Doctoral dissertation, Kent State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1270053064

    Chicago Manual of Style (17th edition)