Comparison of the satiating potencies of cholecystokinin-33 and cholecystokinin-8.

We investigated the satiating potency of CCK-33 and of CCK-8 administered IP to rats prior to a 30-min food intake test using a high-carbohydrate liquid diet. CCK-33 and CCK-8 produced dose-related inhibitions of intake. The ID50S and the slopes of the dose-response functions of the two peptides were not significantly different. We conclude that CCK-33 is as potent as CCK-8 for inhibiting food intake in the rat.

Devazepide antagonizes the inhibitory effect of cholecystokinin on intake in sham-feeding rats.

3S(-)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H-indole-2-carboxamide (devazepide), a potent and selective cholecystokininA (CCKA) antagonist, has been shown to reverse the inhibitory effect of exogenously administered CCK-8 on food intake. In all tests, however, the inhibition of food intake could have been due not only to the CCK-8 administered but also to synergistic interactions between administered CCK-8 and endogenous satiety signals, such as glucagon or CCK released from the small intestine, elicited by the postingestive effects of the test diet. To eliminate these possible interactions, we investigated the effect of devazepide on the inhibitory effect of CCK-8 on the intake of a milk diet during 30 min of sham feeding, a procedure that minimizes or eliminates the postingestive satiating effect of food. Under these conditions, devazepide was a potent antagonist of the inhibitory effect of CCK-8 (16 mumol/kg, IP): The approximate ED50 was 625 ng/kg (1.3 nmol/kg) and the threshold dose was between 62.5 and 625 ng/kg.

Failure to detect increases in brain dopamine metabolism in rats sham feeding sucrose and corn oil.

In a recent study we found that when rats sham fed 6% sucrose, 10% sucrose, and 100% corn oil, the rank order of inhibitory potency for D-1 and D-2 receptor antagonists was 6% sucrose greater than 10% sucrose greater than 100% corn oil. In a complementary study, sham-feeding rats preferred 100% corn oil greater than 10% sucrose greater than 6% sucrose as measured by two-bottle preference tests. The preferences are evidence for the rank order of reward value of these solutions. In the present study we tested the hypothesis that the relative antagonist potencies were due to differential release of DA, dependent on the reward value of the sham-fed solution. Dopamine metabolism, estimated by the ratio of dihydroxphenylacetic acid (DOPAC) to DA, was measured in forebrain-DA terminal fields during sham feeding of 100% corn oil, 6% sucrose, and 10% sucrose. The results did not support our hypothesis: no increase in DA metabolism was observed after the sham feeding of any solution.

Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors.

We studied the effect of fourth intracerebroventricular administration of neuropeptide Y (NPY) and peptide YY (PYY) on ingestive and other behaviors in awake nondeprived rats. Injection of NPY or PYY into the fourth ventricle produced a significant dose-related increase in food intake and reduction in the latency to eat. PYY was more potent than NPY in increasing food intake and decreasing latency to eat, suggesting that PYY-preferring receptors sensitive to the orexigenic effects of NPY and PYY exist in the hindbrain. In addition, both peptides increased water intake when food was present but not when food was absent, suggesting that a neural substrate supporting a direct action of NPY and PYY on water intake is not present in the hindbrain. In time sampling of behaviors occurring during a 90-min feeding test, we found that both peptides increased the time spent eating and reduced grooming. In addition PYY, but not NPY, reduced apparent sleep and increased exploratory activity. This suggests that PYY, but not NPY, influences a hindbrain neural substrate involved in sleep and activity.

D-1 and D-2 receptor antagonists decrease corn oil sham feeding in rats.

Intraperitoneal injection of the highly selective D-1 and D-2 receptor antagonists, SCH 23390 and (-)-raclopride, respectively, produced a dose-related decrease in the intake of corn oil in a 30-min, sham-feeding test. The threshold dose for a significant decrease in intake was 100 micrograms.kg-1 for SCH 23390 and 200 micrograms.kg-1 for raclopride. These doses did not impair rats' latencies to initiate sham feeding, and they did not produce any overt motor deficits. These data, therefore, are consistent with the hypothesis that central dopaminergic activity at both D-1 and D-2 receptors is necessary for the normal processing of the sensory and/or hedonic effects of the oral stimuli produced by corn oil during sham feeding.