Physiological Characterization of REM Sleep in Chronic Alcohol-Exposed Rats

Sri International, Menlo Park CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Alcoholism leads to detrimental alterations to vital organs, including the liver, heart, and brain. Chronic alcoholics show significant deficits in brai morphology accompanied by behavioral alterations leading to addiction, depression, memory deficits, and sleep disturbances. Well-documented sleep problems in alcoholics include, disrupted circadian and ultradian rhythms, insomnia, and parasomnias. Rapid eye movement (REM) sleep is especially vulnerable to the effects of alcohol, and altered REM sleep parameters have been considered significant predictors of relapse in abstinent alcoholics. Additional evidence suggests that the long- term abuse of alcohol affects REM sleep long after alcoholics remain abstinent. Given that alcohol alters inhibitory (GABA) mechanisms and also mediates REM sleep regulation; this neurotransmitter may lead to a crucial link between alcoholism's impact on the neurochemical disruption of vigilance states and REM sleep regulation in particular. The goal of our proposed study is to examine the effects of chronic alcohol consumption on wake and sleep measures in the rat, and additionally address whether GABA mechanisms mediating REM sleep are permanently disrupted by alcohol abuse. Although there are several well- characterized rat models that have provided novel insights into alcoholism's impact on the brain and addictive behavior, research performed on sleep-wake in rodents has provided variable results dependent on animal species, sleep parameters studied, method of ethanol administration, and none have characterized alcohol's impact on the neuronal mechanisms of REM sleep behavior. We hypothesize that chronic ethanol (EtOH) consumption will lead to alterations in spontaneous REM sleep behavior and consequent changes in the REM sleep-regulated brainstem and thalamus of the rat. We will assess the behavioral consequences of long-term EtOH exposure on the electrophysiological characteristics of wake, slow wave sleep, REM sleep, and EEG spectral measures in the standard laboratory rat. Additionally, we will use in vivo microdialysis to assess brainstem and thalamic fluctuations in GABA across the sleep-wake cycle in naive rats, drinking rats and rats that have undergone EtOH withdrawal. The results of these studies will provide insights into the effects of alcohol abuse on sleep-wakefulness and serve as a model for studies evaluating withdrawal and relapse.