Intense cravings which lead to compulsive ingestion of preferred substances are common to the syndromes of bulimia nervosa and compulsive overeating as well as to drug and/or alcohol addiction. These cravings result in relapse in drug dependence and in failure of dietary management of obesity and bulimia nervosa. In the previous proposal, it was hypothesized that an addictive model may be applicable to compulsive eating problems and drug and alcohol dependence. Furthermore, this addictive mechanism may involve endogenous opioid peptides and receptors. Experiments in the present proposal will test the hypothesis that diet preference are mediated in part by opioid mechanisms, and that consumption of preferred foods causes a release of endogenous opioids. This palatability-induced activation of opioid systems may partiality explain the high co-morbidity of compulsive eating disorders and drug abuse. Experiments with rats will determine whether chronic or acute consumption of a preferred or non-preferred diet activates endogenous opioid systems, as reflected in changes in nociception or in changes in the analgesic and feeding responses to morphine. Animal studies will also determine the effects of chronic administration and withdrawal of an opioid agonist (morphine) or an antagonist (naltrexone) on the development and maintenance of diet preferences. Hum studies will also be performed in order to study the subjective aspects of the interactions of opioids, food preferences and craving. Subjective and analgesic responses to the ingestion of food (in this case, ice cream) will be measured in subjects selected for having either a high or a low preference for this food. In methadone patients, food selection and taste preferences will b measured in response to acute methadone withdrawal. In addition, food and taste preferences will be measured during addiction and after discontinuation of methadone. The study of the interactions of diet and opioids in the context of individual differences in baseline diet preferences may provide a basis for improved behavioral, dietary and pharmacologic management of eating disorders and drug abuse.