POTENTIATION OF CCK-8 ON FOOD INTAKE BY ESTRADIOL

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Gonadal steroids are among the numerous factors influencing food intake and body weight in rats. Hormonal effects on these processes are particularly striking in females, which show large increases in food intake and body weight after ovariectomy. These changes can be reversed by peripheral treatment with estradiol or by direct placement of estradiol (E2) in the hypothalamic paraventricular nucleus (PVN). Although it is acknowledged that the effects of E2 on feeding require actions of the hormone within the brain, the neural mechanism by which E2 suppresses food intake remains to be specified. Peripheral injections of the hormone cholecystokinin (CCK) reduce food intake in a number of species, and CCK is now viewed as an important physiological signal for satiety. Manipulation of ovarian hormones has been shown to alter CCK activity in several hypothalamic nuclei, including the PVN, suggesting that the effects of E2 on feeding may be mediated by the modulation of CCK systems within the brain. Along these lines, it has recently been shown that peripheral treatment with E2 potentiates the effects of intraperitoneal (ip) injections of CCK on food intake in female rats. The proposed experiments will attempt to confirm and extend this phenomenon by identifying the brain site at which E2 acts to augment the satiety effect of CCK, and by examining the role played by central CCK receptors in this steroid-peptide interaction. It is hypothesized that E2 enhances CCK activity in the PVN , which in turn potentiates CCK's effects on food intake and mediates the suppressive effects of E2 on eating. The first experiment will evaluate this hypothesis by placing central implants of dilute E2 in the PVN, ventromedial nucleus of the hypothalamus (VMN) and preoptic area (POA)of female rats. It is also hypothesized that the potentiation of the satiety effect of CCK by E2 requires the stimulation of brain receptors for CCK in the PVN. The second experiment will examine the effects of PVN infusions of 2 different CCK receptor antagonists on the suppression of food intake produced by E2 alone, CCK alone and the combined treatment of E2 and CCK. Information obtained from these experiments will contribute to our understanding of brain mechanisms involved in feeding behavior and the ways in which steroid hormones affect brain function.