Opioids represent one set of regulators thought to be involved in eating induced by the rewarding properties of food. Opioid antagonists are particularly effective at decreasing intake of preferred foods including high sucrose and/or high fat foods. For example, we found that extremely low doses of the opioid antagonist naloxone (0.01 mg/kg) decreased intake of a preferred food, whereas much higher dose (3-10 mg/kg) were needed to decrease eating stimulated by energy needs. We also found that dynorphin gene expression was higher in the arcuate nucleus of animals fed a highly palatable diet (high sucrose/fat diet) compared with those fed a less preferred high starch diet. Such data have led us to hypothesize that ingestion of palatable foods (sweet and/or fat) results in an increase in the release of endogenous opioids at brain sites involved in feeding behavior and/or """"""""reward."""""""" We propose four sets of studies to test this hypothesis: Do palatable foods or solutions (containing sucrose, saccharin and/or fat) result in an increase in gene expression of opioid peptides in brain sites known to be involved in feeding behavior or reward? These sites include the nucleus of the solitary tract (NTS), paraventricular nucleus of the hypothalamus (PVN), central nucleus of the amygdala (CNA), ventral tegmental area (VTA) and shell of the nucleus accumbens (s-ACC). Does acute or chronic ingestion of sucrose alter the ability of rats to discriminate morphine? We hypothesize that ingestion of sucrose releases opioids or alters receptor binding/density leading to a change in potency, i.e., a leftward shift in the agonist dose response curve of a rat trained to discriminate morphine. Does chronic ingestion of sucrose result in cellular changes resembling opioid dependence? If sucrose results in the release of opioids one might speculate that rats would display mild opioid withdrawal upon cessation of sucrose availability or following injection of naloxone. We will use cFos immunohistochemistry to observe the pattern associated with chronic sucrose ingestion followed by naloxone injection. Comparison will be made to opioid dependent animals (relatively mild dependence). Must a rat ingest a """"""""critical"""""""" amount of a palatable food before opioids are released? We believe that the reason that naloxone does not affect latency to feeding and only seems to effect maintenance of feeding is that opioids are only released after feeding begins. These experiments address how much food must be eaten (volume, time spent eating etc.) before naloxone administration decreases feeding.

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National Institute on Drug Abuse (NIDA)
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Special Emphasis Panel (ZRG1 (01))
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Lin, Geraline
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University of Minnesota Twin Cities
Internal Medicine/Medicine
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