This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our previous studies demonstrate that the initial response to alcohol, based on subjective and objective measures of brain function that are obtained while carefully controlling the brain's exposure to alcohol, clearly reflect the influence of a family history of alcoholism (FHA). Acute (within-session) tolerance to alcohol also reflected the influence of FHA, but not as strongly, nor in as many measures. We propose to improve our ability to detect the FHA influence on acute tolerance to alcoholism in four ways: 1. We will adopt advances in methodology yielding a clamped BrAC that is established earlier and maintained longer than in our previous studies. 2. We will refine the battery of dependent measures of brain function; substituting objective measures that are highly heritable, reliable, and sensitive to alcohol, for measures that were less effective in previous studies. 3. We will recruit subjects using an improved definition of family history positive (FHP) status. 4. In this study, we will repeat the BrAC clamping session 24 hours later, seeking the amplifying effect, of a second episode of controlled exposure to alcohol, that is often observed in animal studies where it is called rapid tolerance. The time course of BrAC will be identical in each of the 2 clamps that an individual undertakes. The research will be conducted over 5 years and is one of 3 studies funded by NIAAA comprising the Human Genetics Research Component of the recently renewed Indiana Alcohol Research Center (IARC), David Crabb, PI.
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