We are interested in the role that opioids play in the regulation of food intake. It has been known for decades that blockade of the opioid receptor decreases short-term food intake and administration of opioid agonists increases short-term feeding. The manner in which these agents alter feeding is not known. One idea championed by a variety of investigators is that opioids increase the value of food by altering palatability. This concept is substantiated by the following findings: 1) Opioid receptor blockade (naloxone, naltrexone and nalmefene) results in a decrease in the perceived pleasantness of sweet and salty foods and drinks; 2) Naloxone more potently decreases palatable food consumption compared with that of rat chow; 3) Morphine increases intake of a preferred food when presented concurrently with a less preferred food; 4) Consumption of palatable foods alters opioid binding and beta-endorphin content in the hypothalamus of rats; and 5) Ingestion of palatable foods results in a naloxone reversible increase in nociceptive thresholds in rats. The idea that opioids increase the value of food through enhancing palatability lead us to speculate that opioids are involved in the maintenance of the meal, rather than initiation of feeding. Eating might lead to the release of endogenous opioids which would then enhance the value of the food and elongate the meal. To test this hypothesis we propose five sets of studies which address the following specific questions: 1) Are opioids involved in the maintenance of all types of feeding behavior, and if so which opioid receptors are important for such effects? 2) Do opioid antagonists stop a rat from """"""""working hard"""""""" to initiate feeding; or does opioid blockade inhibit a rat from """"""""hardly working"""""""" to maintain food delivery? Also will opioid antagonists block a rat from working """"""""more and more"""""""" to maintain feeding? 3) Do opioids have discriminative stimulus effects similar to the discriminative stimulus effects of agents which initiate feeding? 4) Can the sequence of macronutrient selection help us understand whether opioids are involved in latency or maintenance of the meal? 5) Which brain sites are involved in opioid-induced changes in meal architecture; and are feeding initiating and maintaining sites different? Answers to these questions will help understand whether opioids contribute to the initiation or maintenance of feeding. Such information could eventually lead to the development of pharmacologic agents to treat obesity and other eating disorders.
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