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Chunk #3 — SUBJECTS AND METHODS — Alcohol Administration by Alcohol Clamp

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Role of GABRA2 in moderating subjective responses to alcohol.
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At 10:00 AM, the intravenous infusion of 6% (v/v) ethanol in Ringer’s lactate was begun, using a precomputed rate profile. The profile was derived by forcing a physiologically based pharmacokinetic model of the individual’s alcohol distribution and elimination to follow the desired time course of BrAC as a function of time: a linear ascending limb reaching 50 ± 5 mg/dl at 15 minutes, and then constant for 165 minutes by the method of Ramchandani et al. (1999a). We chose the target level, 50 mg%, as a low to moderate level that would be well tolerated by all subjects without major adverse effects and that would give us measurable effects with sufficient interindividual variance to examine the genetic determinants of interest. Based on serial BrAC measurement, small and intermittent adjustments of the infusion rate were made to maintain the clamped BrAC within 5 mg/dl of the target concentration. After 165 minutes of clamping, the infusion was stopped, the catheter was removed, and the subject was provided with lunch. The BrAC was tracked at 15-minute intervals until it fell below 20 mg/dl