Date of Award

8-2009

Level of Access Assigned by Author

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Advisor

Alan Rosenwasser

Second Committee Member

Harold Dowse

Third Committee Member

Marie Hayes

Abstract

The circadian clock can be affected by a wide variety of drugs, hormones, and environmental conditions. For example, excessive alcohol intake may alter the normal phase (timing) of circadian rhythm, and may even abolish the expression of coherent circadian rhythms in human alcoholics. Further, the negative effects of jet lag and shift work are known to be exacerbated by increased alcohol intake. Alcohol induced alterations in circadian clock function may also contribute to the pronounced mood and sleep disorders that are commonly seen in alcoholics. The circadian rhythms of mammals are mediated by the neurotransmitters GABA and glutamate; GABA and glutamate are major targets of alcohol, increasing the effects of GABA and reducing neuroexcitation caused by glutamate. Previous studies from our laboratory have employed animal models to provide evidence that these effects are due, in part, to direct influences of alcohol on the circadian clock itself. The purpose of this dissertation is to elucidate the effects of chronic ethanol treatment on the circadian pacemaker of the Syrian Hamster and the C57BL/6J mouse. Animals were housed individually in running-wheel cages that allow us to monitor the daily locomotor activity of the mice, under conditions of either voluntary or forced ethanol intake, while control animals were maintained on plain water. Experiment 1 investigated the effects of chronic ethanol treatment on both triazolam- and light-induced phase shifting stimuli in the Syrian Hamster. Experiment 2 examined the effects of chronic ethanol intake on circadian phase shifting evoked by brief light pulses during both early and late subjective night, in mice. We discovered that ethanol reduces the phase shifting effects of triazolam injections, as well as, light-pulses in a phase dependant manner, indicating that ethanol causes a reduction of glutamatergic transmission to the circadian pacemaker. The results of this experiment can shed light on the roles of the neurotransmitters GAB A and glutamate in circadian timing, and will provide new information on the effects of a widely used "recreational" drug, alcohol, on daily activity cycles. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

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