This study was designed to identify the mechanisms underlying the reduction in food intake in rats. Measurements were made of the release of cholecystokinin (CCK) stimulated by potassium chloride in the hypothalamus after (a) γ irradiation (60 Co), (b) treatment with the CCK-A and CCK-B antagonists L-364,718 and L-365,260 with and without radiation, (c) bilateral abdominal vagotomy, and (d) vagotomy with and without radiation and with and without L-364,718. The concentrations of CCK in hypothalamus perfusate were measured by a radioimmunoassay. Exposure of rats to 1, 3, 5 and 10 Gy (1 Gy/min) increased release of CCK in the hypothalamus in a manner that was dependent on dose. A dose of 5 Gy was chosen for further studies. Intraperitoneal (i.p.) administration of 10, 20 and 50 μg/kg of L-364,718 did not induce significant changes in release of CCK in sham-irradiated animals. However, the drug decreased the release of CCK induced by radiation in a dose-dependent manner. In contrast to L-364,718, 20-50 μg/kg of L-365,260 decreased the release of CCK in the hypothalamus in sham-irradiated animals but did not decrease release of CCK induced by exposure to radiation. Vagotomy produced an insignificant reduction in release of CCK compared to that in sham-irradiated controls. However, vagotomy decreased release of CCK in irradiated rats compared to the irradiated rats without vagotomy. Vagotomy and i.p. administration of 10, 20 and 50 μg/kg of L-364,718 decreased release of CCK in irradiated rats compared to that in irradiated rats without vagotomy. However, i.p. administration of 10, 20 and 50 μg/kg of L-364,718 did not induce significant decreases in release of CCK in the hypothalamus of vagotomized and irradiated animals compared to those in rats that were vagotomized and irradiated but not treated with L-364,718. These results demonstrate that radiation increases the release of CCK in the hypothalamus, and that this effect is inhibited by vagotomy and the administration of a CCK-A receptor antagonist. A CCK-A receptor antagonist may be used to mitigate a radiation-induced deficit in food intake.

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