John D. Davis

Analysis of lick rate measure the positive and negative feedback effects of carbohydrates on eating

Previous work has shown that measuring the rate of ingestion of liquid diets, rather than simply volume, reveals important features of ingestive behavior which can help to explain why a particular volume of a liquid is ingested. This study is an extension of that work to a variety of different test solutions. In this study the rate of ingestion of saccharin, two different concentrations of glucose and sucrose and their mixtures with saccharin and seven different concentrations of maltose were measured. The rate functions were fit by the least-squares method to a linear function to determine the intercepts and slope constants. Analysis of how these two parameters changed with the concentration and composition of the test solutions confirms, using different test solutions, a previously reported conclusion that the initial rate of ingestion (the intercept) measures palatability and that the slope constant is a measure of the rate of development of a negative feedback satiety signal.

Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets

A microstructural analysis of the licking behavior of the rat was used to investigate the effects of total abdominal vagotomy on ingestive behavior. Vagotomy decreased the meal size of milk and 3 concentrations of sucrose. The decrease was due to an increase in the decline in the rate of licking during the meal, suggesting that negative feedback from the gastrointestinal tract was enhanced by vagotomy, perhaps because of accelerated clearance of fluid from the stomach to the intestine. No evidence was found for motor dysfunction of licking or alterations in gustatory sensitivity to the test solution. The results suggest that vagotomy enhanced the strength of an extravagally mediated negative feedback signal from the intestine and that the vagus nerve normally prevents this from occurring by regulating gastric clearance.

The impact of milk-derived unconditioned and conditioned negative feedback on the microstructure of ingestive behavior

We describe at the microstructural level the impact of unconditioned and conditioned negative feedback on the licking behavior of the rat. Six groups of rats were trained to ingest one of six different dilutions of sweetened milk (0.5:1, 1:1, 2:1, 4;1, 8:1, and 16:1, water to milk ratios) under real feeding conditions until intake was stable. Then they were given five sham-feeding tests with the same solution. We compared the size of the clusters (SC) and their number (NC) during the 15-min period when intake rate was declining in the real-feeding test with SC and NC during the corresponding 15-min period in the following sham-feeding test. Intake increased significantly over the five sham-feeding tests with the two highest concentrations, indicating the extinction of conditioned negative feedback. With these two solutions, we compared the microstructure of licking behavior in the first with that in the fifth sham-feeding test to determine if conditioned negative feedback affected SC or NC or both. The effect of both unconditioned and conditioned negative feedback on licking behavior was to decrease the number of clusters without affecting their size. We conclude that negative feedback derived from the accumulation of milk in the gastrointestinal tract decreases the probability of initiating a bout of licking during a pause. It has no effect on the ability to continue a bout of licking once it has begun.

Cholecystokinin changes the duration but not the rate of licking in vagotomized rats.

Abdominal vagotomy markedly reduces or abolishes the inhibitory effect of cholecystokinin (CCK-8) on meal size. To investigate the rate and microstructure of licking underlying this phenomenon, licking was measured throughout a meal of milk in intact and vagotomized rats after intraperitoneal injections of isotonic saline or CCK-8. CCK-8 increased the slope of the decay of licking, decreased the efficiency of licking, and decreased the duration of licking in intact rats but had no effect on either the slope of the decay of licking or the efficiency of licking, but it increased the duration of licking in vagotomized rats. These results demonstrate that abdominal vagal nerves are necessary for CCK-8 to increase the rate of decay of licking, but nonvagal mechanisms mediate the effect of CCK-8 on duration of licking.

Corticotropin-releasing factor decreases meal size by decreasing cluster number in Koletsky (LA/N) rats with and without a null mutation of the leptin receptor

The homozygous mutant Koletsky rat is a monogenic form of obesity and hyperphagia due to a null mutation of the leptin receptor (lepr(fak)). To investigate if the lack of leptin action on the brain of homozygous mutants affected the inhibitory potency of corticotropin-releasing factor (CRF) on meal size, artificial cerebrospinal fluid or one of five doses of CRF was administered through third ventricular cannulas in 8 +/+, 10 +/fa(k), and 8 fa(k)/fa(k) rats 15 min before access to 20% sucrose in lickometer tubes for 30 min. CRF had equivalent inhibitory potency in fa(k)/fa(k) and +/+ rats. Thus, the complete lack of leptin action in fa(k)/fa(k) rats did not change the inhibitory potency of CRF. CRF was significantly more potent, however, in +/fa(k) rats than in the other two genotypes. Thus, the heterozygote condition of this mutation did not function as a classical recessive mutation for this behavioral phenotype. Despite these differences in potency, microstructural analysis revealed that CRF decreased intakes in all three genotypes by decreasing the number of clusters of licking without changing the size of clusters.

Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive behavior of rats.

Intact and abdominally vagotomized rats were offered for ingestion during a 30-min period a saccharin and glucose solution or another with 0.1 M mannitol added. The addition of mannitol to the test solution caused a large reduction in intake of intact rats caused by a very rapid decline in the rate of licking during the test. This did not occur with the vagotomized rats. This demonstrates that abdominal vagal nerves are necessary for the inhibitory effect of mannitol on the ingestive behavior of rats. Vagotomized rats also differed from the intact ones by ingesting less of the mannitol-free solution. This was suggested to result from accelerated gastric clearance, leading to abnormally rapid stimulation of negative feedback from the small intestine conveyed to the CNS by extravagal pathways.

Increase in intake with sham feeding experience is concentration dependent

Most sham feeding studies show that about three sham feeding tests are required for intake to reach maximum. One study, however, using a dilute solution, reported maximum sham intake in the first sham feeding test, suggesting that the progressive rise in sham intake may be concentration dependent. We tested this hypothesis with six groups of rats given five sham feeding tests each with one of six concentrations of sweetened condensed milk (0.5:1, 1:1, 2:1, 4:1, 8:1, 16:1, water-to-milk dilutions). It took three sham tests for intake to reach maximum with the three most concentrated solutions, but only one with the three weakest. Thus the intake of concentrated solutions of milk is limited by two negative feedback signals, one derived from the accumulation of fluid in the gastrointestinal tract, the other from a labile signal that loses its effectiveness with sham feeding experience. In contrast, the intake of weak concentrations is limited only by the nonlabile negative feedback signal because the labile signal is missing.Most sham feeding studies show that about three sham feeding tests are required for intake to reach maximum. One study, however, using a dilute solution, reported maximum sham intake in the first sham feeding test, suggesting that the progressive rise in sham intake may be concentration dependent. We tested this hypothesis with six groups of rats given five sham feeding tests each with one of six concentrations of sweetened condensed milk (0.5:1, 1:1, 2:1, 4:1, 8:1, 16:1, water-to-milk dilutions). It took three sham tests for intake to reach maximum with the three most concentrated solutions, but only one with the three weakest. Thus the intake of concentrated solutions of milk is limited by two negative feedback signals, one derived from the accumulation of fluid in the gastrointestinal tract, the other from a labile signal that loses its effectiveness with sham feeding experience. In contrast, the intake of weak concentrations is limited only by the nonlabile negative feedback signal because the labile signal is missing.

Orosensory stimulation is sufficient and postingestive negative feedback is not necessary for neuropeptide Y to increase sucrose intake

Although central administration of neuropeptide Y (NPY) has a potent orexic effect, it is not clear how NPY changes the potency of peripheral feedbacks from the gut to prolong eating and increase meal size. It has been suggested that NPY increases the stimulating effect of orosensory sweet stimuli or that it decreases the inhibitory effect of postingestive stimuli. To clarify this issue, we compared the orexic effect of NPY (2 microg) injected into the third ventricle of the brain on the volume and microstructure of intake of 0.8M sucrose during sham feeding (SF) and real feeding (RF) in male Sprague Dawley rats. The rationale for this comparison is that orosensory stimulation occurs in SF and RF, but postingestive negative feedback is present only in RF. NPY increased the volume ingested and the rate and number of clusters of licking significantly more in SF than in RF. This demonstrates that orosensory sucrose stimulation is sufficient and postingestive negative feedback is not necessary for the orexic effect of NPY under these experimental conditions.

The control of water and sodium chloride intake by postingestional and orosensory stimulation in water-deprived rats

We investigated the role of oropharyngeal and postingestional stimulation in the control of the intake of water and NaCl solutions by testing water-deprived rats under real- and sham-drinking conditions with water, 0.150, 0.225, and 0.300 M NaCl solutions. A series of real-drinking tests was given until intake stabilized followed by a series of sham-drinking tests with the same solution. When sham intake stabilized the concentration was increased and the series of real- followed by sham-drinking tests was repeated. Intake of water and 0.150 M NaCl in the first sham-drinking test was significantly greater than in the preceding real-drinking test and did not change with real- or sham-drinking experience. In contrast, intake of 0.225 and 0.300 M NaCl in the first sham-drinking test was not significantly greater than in the preceding real-drinking test but increased with sham-drinking experience. Real intake of 0.225 and 0.300 M NaCl following sham-drinking experience with a lower concentration declined significantly with real-drinking experience. These results show that postingestional stimulation plays a direct role in the control of the intake of water and isotonic saline with little or no orosensory contribution. In contrast, conditioned orosensory responsiveness played the central role in the control of the intake of the two hypertonic solutions with little or no direct contribution from postingestional stimulation. Postingestional stimulation, however, played an indirect role by serving as the unconditioned stimulus for the conditioned orosensory control.

A behavioral analysis of the ingestion of glucose, maltose and maltooligosaccharide by rats

Glucose, maltose, and Polycose are stimuli that differ in their effectiveness in stimulating ingestion in the rat. To understand better how variation in glucose chain length affects the ingestion of these compounds, we compared the effect of six concentrations of glucose, maltose, and maltooligosaccharide (MOS) on the microstructure of the licking behavior of the rat. At the three lowest concentrations the order of effectiveness in stimulating ingestion was MOS > maltose > glucose. At the three highest concentrations, there were no differences among the three compounds in volume ingested. As measured by initial rate of licking, the orosensory stimulating effectiveness of the three compounds were ordered as MOS > maltose > glucose. The magnitude of the negative feedback signals were very similar for MOS and maltose and greater than glucose at all but the highest two concentrations of glucose, suggesting that glucose chain length, not caloric density, is responsible for the differences in the magnitude of negative feedback. With the three lowest concentrations, the ordering of the compounds in their ability to stimulate intake depended on orosensory stimulating ability.