The aim of this study is to determine whether increased risk for alcoholism is associated with differences in the functional sensitivity of the GABA A- benzodiazepine receptor system. Alcoholism is in part genetically determined. Sons of alcoholic fathers, who are at particularly high risk for alcoholism, appear less sensitive to the effects of ethanol than are control subjects. Since ethanol affects membrane fluidity and numerous neurotransmitter system , the reason for this apparent subsensitivity remains to be determined. Ethanol increases chloride conductance at the GABA A-benzodiazepine receptor, thus potentiating GABAergic neurotransmission. Animal studies have implicated effects of ethanol on the GABA A-benzodiazepine receptor system in ethanol intoxication, tolerance, and dependence. However, the role of this receptor system in vulnerability to alcoholism has not yet been examined. Since the GABA A receptor is the primary site of action of benzodiazepines, this study will use the effects of acute administration of diazepam as a specific measure of receptor function. Diazepam effects will be assessed in sons of alcoholics and control subjects using reduction in saccadic eye movement velocity (SEMV), a reliable, quantitative, dose-dependent index of GABA A-benzodiazepine receptor function, as well as self-rated sedation and intoxication, memory, epinephrine, and norepinephrine. Findings of differences in benzodiazepine sensitivity in sons of alcoholics versus controls may provide a possible neurochemical basis for subsensitivity to ethanol in son of alcoholics and a potential biologic marker linked with the actions of ethanol at the receptor level. Differences between sons of type 1 versus type 2 alcoholics and those with multiple versus a single (i.e. their father) alcoholic relative will also be assessed.
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| Cowley, D S; Roy-Byrne, P P; Radant, A et al. (1994) Eye movement effects of diazepam in sons of alcoholic fathers and male control subjects. Alcohol Clin Exp Res 18:324-32 |
| Cowley, D S; Roy-Byrne, P P; Godon, C et al. (1992) Response to diazepam in sons of alcoholics. Alcohol Clin Exp Res 16:1057-63 |
