A preliminary study of acute responses to clamped alcohol concentration and family history of alcoholism

Background: The clamping method of alcohol administration was combined with a battery of dependent measures of frontal lobe brain function, and a nove l index of acute adaptation, in a preliminary study in order to explore the paradigm's sensitivity to a familial history of alcoholism (FHA). Methods: Ten family history-positive (FHP) and 10 family history-negative ( FHN) adult social drinkers of both genders underwent alcohol clamping. Twen ty minutes after the start of an intravenous infusion of alcohol, the breat h alcohol concentration was clamped at a target of 60 +/- 5 mg/dl for 150 m in. Initial and adaptive responses to alcohol were assessed using scalar in dices of change. One index assessed initial improvements or impairments in brain function after alcohol. The other index assessed acute adaptation (to lerance or sensitization) to alcohol while the brain's exposure to alcohol was held constant. The battery of dependent measures included subjective pe rceptions, neuropsychological tests, saccadic eye-movement tasks, and event -related potential (ERP) tasks. Effect sizes for FHA were estimated for 10 dependent variables that showed adequate baseline test-retest reliability ( r > 0.6). Results: FHP subjects showed less intense initial responses to alcohol in s ubjective perceptions, but greater changes in the latency of volitional sac cades and ERP P3 components than did the FHN controls. FHP subjects general ly showed greater acute tolerance to alcohol than did controls, who showed more instances of acute sensitization at this moderate breath alcohol conce ntration. Effect sizes for FHA exceeded 0.4 in more than half of the indice s. Conclusions: The BrAC clamping paradigm assesses initial and adaptive respo nses of a battery of behavioral and electrophysiological measures of fronta l lobe function to ethanol that appear both reliable and sensitive to FHA.