Component 28 has three phases. The first phase is a continuation of a study that prospectively compares the EEG activity and psychological symptoms of 30 alcohol-dependent patients, assessed after 1, 2, and 8 weeks of abstinence, to 20 matched nonalcoholic controls, assessed over a comparable period. This study is also designed to evaluate abnormalities in the EEG activity and psychological status of alcohol dependent patients as predictors of their outcome (i.e., relapse vs. continued abstinence). It is hypothesized that the severity and persistence of EEG and psychological abnormalities will be associated with a decreased latency to or increased likelihood of relapse. The second phase of this component is a new study that will examine benzodiazepine/GABA receptor sensitivity in abstinent alcoholics. For this purpose, we will intravenously administer a subhypnotic dose of the benzodiazepine, midazolam, and a placebo to 20 alcoholics who have remained abstinent for 3 weeks. For comparison purposes, these drugs will also be administered to 20 nonalcoholic controls. The general hypothesis states that abstinent alcoholics will exhibit electrophysiological and subjective signs of reduced benzodiazepine sensitivity, relative to normal controls. The third phase of the component will examine the ability of the benzodiazepine antagonist flumazenil to restore benzodiazepine sensitivity to normal levels in abstinent alcoholics. For this purpose, we will pretreat groups of abstinent alcoholics and normal controls with either 1.5 or 15 mg flumazenil or placebo. On the following day, all subjects will receive an IV dose of midazelam and complete the same test battery used in Phase 2. The general hypothesis states that normal controls will show no change in test performance as a result of flumazenil treatment. Flumazenil is expected to restore the test performance of alcoholics to control group levels. The three phases of component VI constitute a program of research designed to improve our understanding of the biological substrates of alcohol dependence and their relevance to relapse.
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