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. 1.Neuroendocrine measures of opioid activity in alcohol-dependent subjects will be diminished immediately following acute alcohol withdrawal (day 5) relative to age-matched controls and will increase during early abstinence (day 30) approaching control levels. 2.PET-derived mu and delta opioid receptor density will be elevated imediately following acute alcohol withdrawal (day 5) relative to age-matched controls and will decrease during early abstience (day 30) approaching control levels. This receptor density elevation reflects a compensatory increase i response to low opioid activity. 3.Alcohol craving will positively correlate with mu-and delta-receptor density and the ASN/ASP mu opioid receptor polymorphism. Craving will negatively correlate with neuroendocrine measures of opioid activity. 4. The ASN/ASP mu opioid receptor polymorphism will be associated with naltrexone treatment effectiveness, and will predict those patients who are most likely to relapse during or immediately following naltrexone treatment. 5. High alcohol craving, elevated mu and delta receptor density, the ASN/ASP mu opioid receptor polymorphism and high opioid sensitivity will be negatively associated with naltresone treatment effectiveness, and will predict those patients who are most likely to relapse during or immediately following naltrexone treatment. This protocol represents the integration of three NIH-funded RO1 applications (Frost, RO1-AA11872; Wand, RO1-AA12303, McCaul, RO1-AA11855). We will study a common pool of subjects who will participate in a comprehensive characterization of opioid system and opioid medication efficacy. This protocol will accomplish five specific aims: 1. To examine neuroendocrine measures of endogenous opioid activity immediately following alcohol withdrawal (5 day), through early abstinence (30 day) and following naltrexone dose induction. 2. To examine PET-derived measure of mu- and delta-opioid receptor density immediately following alcohol withdrawal (5 day), through early abstinence ( 30day) and following naltrexone dose induction. 3. To examine subjective measures of craving, mood and alcohol withdrawal severity during alcohol withdrawal (5 day), through early abstience (30 day) and following naltrexone dose induction. 4. To examine the realtionship of the ASN/ASP mu opioid receptor polymorphism to neuroendocrine, PET and subjective measures associated with the opioid system. 5. To esamine the utility of mu-and delta-opioid receptor polymorphism and subjective measures associated with alchold withdrawal and craving as predictors of medication effectiveness during outpatient naltrexone treatment.
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