ROLE OF ENDOGENOUS OPIOIDS IN NORMAL AND STRESS-RELATED FEEDING BEHAVIOR
Abstract
Previous work in this laboratory indicated that in rats the opiate antagonist, naloxone, produced a dose-related decrease in nocturnal feeding as well as the hyperphagias induced by food deprivation (FD) and 2-deoxy-D-glucose (2-DG; a glucose anti-metabolite). In contrast, insulin-induced feeding was not suppressed by naloxone (Lowy et al., 1980). Subsequent work indicates that the anorexic effect of opiate antagonists is stereoselective and not due to a secondary effect on water intake. Moreover, administration of opiate agonists, such as morphine, ketocyclazocine and loperamide stimulate feeding in non-deprived rats. Additional studies were designed to evaluate which endogenous opioid (EO) may be involved in the naloxone-sensitive hyperphagic conditions. Administration of dexamethasone (DEX), a glucocorticoid which depletes the releasable stores of pituitary (beta)-endorphin-immunoreactivity ((beta)-EP-ir), produced a feeding profile similar to that observed in naloxone-treated rats. In addition, plasma (beta)-EP-ir levels were elevated 2-3-fold during various hyperphagic conditions in rats, such as nocturnal-, 2-DG- and FD-induced feeding. However, further studies suggest that elevations in plasma (beta)-EP-ir are not necessary for the initial 1 hour feeding response following 2-DG administration. An important outcome of our initial study with naloxone was the suggestion that the glucoprivic agents, 2-DG and insulin, operate through opiate dependent and independent mechanisms, respectively. In support of this hypothesis, normal hamsters selectively increased feeding in response to insulin, but not 2-DG administration. In addition, the long-lasting opiate antagonist, naltrexone, failed to decrease hamster feeding. Moreover, hamsters are resistant to the appetite stimulating effects of opiate agonists. These results suggest that the glucoprivic agents, 2-DG and insulin, may be useful tools to monitor opiate involvement in feeding behavior. In conclusion, EO appears to be involved in normal feeding behavior, as well as stress-induced feeding changes. As such, pharmacological manipulation of the EO system may be a useful therapeutic means of controlling pathological feeding states.
Degree
Ph.D.
Subject Area
Pharmacology
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