The experiments proposed in this application will establish the role of dietary variables in 1) modulating the behavioral actions of opiate drugs, and 2) altering the functioning of the endogenous opioid system in rats. It is hypothesized that the intake of palatable sugars and/or fats increases endogenous opioid levels and/or opiate receptor binding affinity which in turn modifies the actions of exogenous opiates on behavior. This proposal will investigate the role of sucrose, saccharin and dietary fats on pain sensitivity and opioid-induced analgesia using both the tail flick and hot plate tests. Initial studies will delineate which aspect of these nutritional variables are most important for their impact on opioid-mediated behaviors. Studies investigating the role of pre- and post-ingestive effects of diet will indicate whether the taste of palatable substance is a sufficient stimulus for altering pain sensitivity or if ingestion of the solution is required. The pharmacological processes underlying dietary modulation of opioid drug actions will be addressed in studies investigating the effects of diet on the actions of selective peripherally and centrally administered opioid agonists and antagonists. Additionally, the effects of diets on opiate receptor binding will be determined in vivo using """"""""apparent"""""""" pA2 values. The endogenous opioid systems has been implicated as important in mediating a variety of behaviors, as well as responses to noxious stimuli. Studies will be conducted to assess if diet can also alter the effects of opiate drugs on these behaviors. For example, it has been hypothesized that eating palatable foods activates the endogenous opioid system which may stimulate further intake of appetizing foods. This hypothesis will be tested y examining the effects of opiate agonists and antagonist on energy intake in rats given prior exposure to palatable foods. Diet also may moderate the experiences of drug tolerance and withdrawal. To address this issue, the effects of diet on the development of tolerance and the symptoms of withdrawal and precipitated abstinence will be tested. A unique relationship exists between palatable foods and both exogenous and endogenous opioids. This relationship has implications for a number of clinical problems including pain management, eating disorders and drug addiction. Opiate drugs are among the most potent pain relievers. However, they tend to be administered in less than effective doses because clinicians are concerned about the potential for tolerance and addiction. The relationship between diet and opiate drugs has important implications for the basic understanding of the endogenous opioid system. The studies proposed in this application also raise the possibility that simple dietary manipulations could be valuable in the treatment of a variety of drug-related problems.
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