The benzodiazepine-GABA-chloride ionophore receptor complex has been demonstrated to be involved in the physiologic and psychologic effects of ethanol. Diazepam, a benzodiazepine, binds to this receptor complex, and demonstrates a cross-tolerance to ethanol. Recent studies have shown that diazepam-induced alterations in eye movements offer a useful measure of benzodiazepine receptor sensitivity in humans. Preliminary findings at the NIMH and NIAAA suggest an increased sensitivity to the effects of diazepam, as measured by saccadic eye movements, in alcoholics. This increased sensitivity appears to persist despite long-term abstinence (up to four years). This may suggest either long-term toxic effects of ethanol upon the benzodiazepine receptor or an alteration in the receptor that is present prior to the onset of alcohol abuse. In this study we continue our studies of diazepam sensitivity in alcoholics as well as evaluating if this increased sensitivity to diazepam is present in persons """"""""at-risk"""""""" for the development of alcoholism compared to persons without a family history of alcoholism. Subjects will also be evaluated for EEG, ERP (event- related potentials), body sway, vigilance, tracking, memory, mood assessment and expectancy, ACTH, cortisol, prolactin, and growth hormone response to diazepam. The first part of this protocol has been completed. A total of eight alcoholics and ten age and sex-matched controls have been assessed and the results are now being analyzed. This study should be written up in the next few months and on the basis of the results a decision will be made as to whether to continue the project to study high risk subjects (children of alcoholics).
