SLEEP DISTURBANCES AFTER CHRONIC ALCOHOL CONSUMPTION: HOMEOSTATIC DYSREGULATION OR CIRCADIAN DESYNCHRONY?

Rong Guo

Chronic alcohol use often leads to sleep disturbances such as insomnia and sleep fragmen¬ta¬¬tion, but the underlying mecha¬nisms are not fully understood. Sleep is regulated by two main processes: a homeo¬static process representing the build-up of sleep pressure during wake and a circadian pro¬cess integrating sleep timing with environmental cues. It is possible that chronic alcohol exposure impairs sleep through either process or both. This dissertation presents investi¬gations to address these possibilities. We first determined if chronic alcohol exposure impaired the homeostatic regulation of sleep by using a sleep deprivation challenge. We found that alcohol-treated rats showed robust and relatively normal compen¬satory increase in sleep time and sleep intensity (as measured by slow wave amplitude) within 24 hours after the challenge, but the recovery sleep of these rats was delayed and fragmented. These results suggest that chronic alcohol exposure may weaken the stability of sleep states, leading to sleep fragmentation, but the homeostatic regulatory mechanisms were most likely intact. We next determined if chronic alcohol treatment altered the integrity of circadian systems by examining diurnal rhythms of body temperature, locomotor, plasma corticosterone, and Per1 expression in the master pacemaker (suprachiasmatic nucleus, SCN) and in the HPA axis (pituitary and adrenal glands). We found that after chronic alcohol exposure these processes still exhibited a 24-hour cycle, but the cycles were less robust and more variable. Most importantly, the phase relationships among diurnal physiological rhythms, and between the central and peri¬pheral molecular clocks, were significantly altered leading to desynchronized circadian processes. Lastly, we placed rats under constant darkness to remove the external light Zeitgeber and found that constant darkness stabilized the dampened rhythms and normalized the blunted distribution of sleep/wake time caused by chronic alcohol exposure. Taken together, our studies suggest that chronic alcohol exposure: 1) weakens the stability of sleep states leading to unstable and fragmented sleep, 2) compro¬mises the ability of SCN to synchronize internal clocks and to integrate sleep timing with the external light Zeitgeber, and 3) does not prevent the animal from responding to the build-up of sleep pressure.

SLEEP DISTURBANCES AFTER CHRONIC ALCOHOL CONSUMPTION: HOMEOSTATIC DYSREGULATION OR CIRCADIAN DESYNCHRONY?

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