OPIOID PEPTIDES: FOOD INTAKE, SELECTION AND OBESITY

Recent research has implicated the endogenous opioid peptides in the regulation of food intake. Morphine, which is believed to facilitate endogenous opioid activity, and the endogenous opioids themselves lead to increases in food intake. In contrast, naloxone, which is though to inhibit endogenous opioid activity leads to decreases in food intake. Moreover, these pharmacological agents act in opposition on patterns of diet selection in rats given access to the three macronutrients: fat, protein and carbohydrate. While morphine administration results in an increase in fat intake and a suppression in carbohydrate and protein intakes, naloxone administration results in a suppression of fat intake with no modifications in protein or carbohydrate. Additional support for the role of endogenous opioid involvement in the regulation of food intake comes from the observation that animals with different forms of experimental obesity have different brain and pituitary levels of the endogenous opioid peptide, beta-endorphin. Interestingly, these animals also display different patterns of diet selection. The present grant will investigate furthe the interaction between opioid peptides and feeding behavior and diet selection in normal animals and animals with different forms of experimental obesity. First, patterns of caloric intake and dietary self-selection will be determined in animals with different forms of experimental obesity including genetically obese animals, animals made obese by the neonatal administration of monosodium glutamate, animals made obese by the destruction of the ventromedial hypothalamus and animals with dietary-induced obesity. Second, the interaction between opioids and food intake will be explored by examining central and peripheral mediation of opioid effects on feeding behavior, determining opioid effects on body weight gain and food utilization, and investigating the effects of modifying diet composition on the animal's response to opioids. Information gained from the studies on the interaction between opioids and feeding behavior may help delineate factors contributing to the development of obesity and give insights into mechanisms underlying the regulation of food intake.