Measuring a brain function while maintaining a constant breath alcohol concentration (BrAC) demonstrates acute tolerance to alcohol if the function recovers towards its baseline value during the steady state. GCRC-sponsored pilot studies produced a method for adjusting the intravenous infusion rate of alcohol in order to close the gap between the current BrAC and an a priori target. To date, we have demonstrated that the """"""""clamping"""""""" paradigm is useful for acute tolerance studies beginning 45 minutes after beginning oral alcohol administration at a target level of 5015 mg%. Further, the rate of alcohol administration in the clamped and equilibrated steady state yields a direct measure of the alcohol elimination rate (AER) with high test/retest reliability. The NIAAA has awarded a R21 grant to shorten the time required to achieve the beginning of the steady state BrAC (""""""""start time"""""""") and to identify brain measures showing acute adaptation to alcohol that depend on the magnitude of the steady-state BrAC. Two small studies are proposed in order to complete the grant. First, one sample (N=10) is employed once to optimize the new iv induction method and another sample (N=10) is tested twice at 60mg% in order to compare the results of the iv induction to the existing (oral loading) method. Then, using the most reliable method, separate clamping sessions are conducted at target BrACs of 0, 40 and 80mg% in each of 20 additional subjects.
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