The goal of this project is to examine the effect of naltrexone, an opioid antagonist, on voluntary alcohol consumption in nontreatment seeking alcohol dependent volunteers using a laboratory self-administration paradigm. The specifics are: 1) to determine whether subjects on naltrexone exhibit greater reductions in voluntary alcohol consumption than subjects on placebo; 2) to determine whether naltrexone modifies the subjective and neuroendocrine responses to alcohol; 3) to evaluate whether the subjective and neuroendocrine responses to alcohol predict further voluntary alcohol consumption; and 4) to determine whether naltrexone affects voluntary alcohol consumption and responses to alcohol differently for men and women and ; 5) to determine if naltrexone alters anxiety in response to a stressor. We have recruited 37 subjects so far, of which 32 subjects have successfully completed both laboratory sessions. In a preliminary analyses of the data from the first 21 subjects, naltrexone was found to suppress alcohol-induced release of ACTH and cortisol and increases in heart rate and blood pressure, but we did not find differences in the number of drinks chosen in the two lab sessions or in indices for """"""""craving"""""""". We felt that the strength of the current paradigm lies in the use of low doses of alcohol, the use of an alcohol dependent sample rather than social drinkers. However, this paradigm also has some limitations such as the lack of powerful alternative reinforcers and the need for an alternative """"""""craving"""""""" assessment scale which would balance brevity and reliability of assessments. Therefore we have modified the current paradigm and are piloting a new third laboratory session which provides subjects with the opportunity to either drink up to 8 drinks or chose to obtain the monetary value of each drink. This new protocol may be more sensitive to changes in number of drinks consumed and """"""""craving"""""""" for alcohol. Our overall plan has not changed substantially, We hope to recruit and complete running 25-30 subjects this year.
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