The main objective of the proposed research is to elucidate the relationship between steroid effects on hypothalamic cholecystokinin (CCK) and the hypothalamic regulation of food intake (FI). Although the ventromedial nucleus of the hypothalamus (VMH) is considered the primary CNS site of both steroid and CCK effects on FI, we plan to identify all hypothalamic areas which contain steroid accumulating, CCK-positive neurons, to elucidate the functional nature of this interaction in vitro, and to determine the effects of steroids and CCK on FI. Steroid autoradiography and CCK immnunohisto-chemistry will be combined to determine which CCK-containing neurons bind steroids, providing a morphological basis for the interaction of steroids and CCK-neurons. Hypothalamic areas identified in the morphological studies as having an overlap of steroid-binding and CCK-immunoreactive staining will be microdissected from rats in which the reproductive cycle and pattern of FI have been monitored. The tissue will be used for in vitro superfusion experiments which will determine if steroids act primarily at the level of the CCK cell body or terminal. Moreover, this approach will enable us to detemine if steroids stimulate or inhibit the release of CCK or whether they modulate CCK release in response to other neuroactive agents such as opiates and GABA. Since tissue will be removed from intact or gonadectomized males, females, androgenized females and neonatally castrated males CCK levels and patterns of release can correlated with gonadal hormone environment and FI. A direct measure of the effects of steroids on CCK levels and FI will be done in parallel group of animals in which the cerebrospinal fluid and plasma levels of CCK will be monitored. Finally the effect of CCK or anti-CCK serum on the FI pattern of these animals will be assessed. It is expected that the study of the morphological and functional interaction of steroids and CCK neurons will identify the neurochemical structures which regulate feeding behavior and will prove particularly valuable in promoting the general understanding of this complex area of physiology.
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