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Wake Forest Researchers Find Brain Region "Exquisitely" Sensitive to Alcohol

WINSTON-SALEM, N.C. – Wake Forest University School of Medicine scientists are closing in on why drinking alcohol before bedtime paradoxically improves sleep that evening, but disrupts sleep during the early morning hours.

In a presentation at the Research Society on Alcoholism in San Francisco, Dwayne W. Godwin, Ph.D. explained that a key brain region involved in sleep, the thalamus, is "exquisitely sensitive to alcohol."

The cells in the thalamus possess an ion channel that behaves differently depending on the amount of alcohol that has been drunk. "Low doses of alcohol increase activity; high doses shut it down," said Godwin, associate professor of neurobiology and anatomy.

Characteristic "spindle" brain waves are produced during what is called stage II sleep, which is transiently enhanced after alcohol consumption but is reduced later in the night . The spindle waves are generated in the thalamus and picked up in brain wave recordings.

Godwin and colleagues Breck Carden, Ph.D., Jian Mu, M.D., and Nuwan Kurukulasuriya, Ph.D. in the Center for the Neurobehavioral Study of Alcohol are using the ferret as an animal model for sleep. The ferret thalamus produces the same characteristic spindle waves during stage II sleep as in people and reacts differently depending on the amount of alcohol.

"Despite widespread interest in the influence of alcohol on sleep, the influence of alcohol on the thalamus had been uncharted territory," he said. Use of the ferret thalamus "is optimal for exploring such mechanisms, because they possess all of the necessary circuitry for the generation of spindle waves, which allows us to translate our studies to the situation in humans." Godwin said human studies have shown that just one drink before bed may decrease the time it takes to fall asleep. But in the second half of the night, sleep often is disrupted. "You may tend to wake up more and be a little more restless."

When watched in the sleep laboratory, a drink before bed increases stage II sleep in the first part of the night and decreases that sleep in the second part of the night.

In alcoholics, however, the decrease in stage II becomes more permanent. "Sleep disturbances are common in alcoholic patients, with a number of serious health consequences," Godwin said. "Chronic consumption can lead to a cycle where alcoholics increase their alcohol consumption in order to improve the subjectively more satisfying patterns of sleep," he said.

The disrupted sleep pattern in alcoholics continues even into abstinence following treatment. "There is a significant relationship between alcoholics returning to consumption because of this sleep issue." In other words, one reason they go back to drinking may be an attempt to make their sleep feel more normal, or satisfying. In the animal model, the equivalent of a small bedtime dose of alcohol leads to enhancement of sleep early in the sleep period and disruption later in sleep. Godwin said that the ion channels underlie normal sleep spindles are functioning normally early in sleep, and but may be turned off later in sleep -- corresponding to those later periods of human sleep that are less restful.

The ion channels are pores or passageways through the cell membranes of the neurons in the brain. Godwin and his colleagues are focusing on channels through which calcium ions flow from one side of the membrane to the other. The calcium ions carry an electrical charge and the charge "helps to determine whether or not the cell that possesses that channel will communicate with the next cell down the line in the chain of neurons."

It is the calcium channels where the reaction differs depending on whether the thalamus is exposed to low doses or high doses of alcohol. "This channel is exquisitely sensitive to alcohol."

The next step is to expose the ferret thalamus to continuing high doses of alcohol -- paralleling an alcoholic''s consumption. "We are now exploring whether chronic consumption of alcohol may turn this channel off, not just acutely, but permanently," Godwin said.

That permanent shutdown could explain why recovering alcoholics have trouble sleeping, and finding a means to alleviate it may help on the path to recovery.

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