Biomedical subjects

S E Swithers

Publications and source records attributed to S E Swithers.

17 recordsLinked to original sources

PubMed2004

A Pavlovian approach to the problem of obesity.

During the past 15-20 y, the incidence of overweight and obesity in the United States has grown rapidly. The processes that underlie this alarming trend remain largely unspecified. We hypothesize that degradation of the ability to use certain orosensory cues to predict the caloric consequences of intake may contribute to overeating and excessive weight gain. The results of two preliminary studies with rats are consistent with this hypothesis. In one study, the ability of rat pups to regulate their caloric intake after consuming a novel high-calorie, sweet food was disrupted if they had received prior training with sweet tastes that failed to predict the caloric consequences of eating. Another study found that altering the normal predictive relationship between food viscosity and calories led to increased body weight in adult rats. Dietary factors that degrade the relationship between sweet tastes, food viscosity and calories may contribute to overeating and weight gain.

Animals↗

PubMed2001

Gastrointestinal projection maps of the vagus nerve are specified permanently in the perinatal period.

The vagal innervation of the proximal gastrointestinal (GI) tract is lateralized. To determine whether this pattern is specified as early as the perinatal period, neonatal rat pups were given unilateral cervical vagotomies. Separate groups received (1) transections below the left nodose ganglion, (2) left cervical resections that included removal of the nodose ganglion, or (3) sham surgeries. At 4 months of age, each animal's vagal afferent projections from the unoperated side were mapped by injecting the nodose with WGA-HRP, preparing the stomach as wholemounts, and processing the tissue with tetramethyl benzidine. The two types of vagal afferent endings in GI smooth muscle, namely intraganglionic laminar endings and intramuscular arrays, were surveyed separately, and their regional distributions were mapped. Changes in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNX) were assessed with cell counts and area measurements. Neonatal loss of the vagus innervating one side of the GI tract, with or without ganglionectomy, did not cause the unoperated vagus to sprout to the denervated side. In addition, removal of the projections to the one side of the target organ did not produce a reorganization of the projection maps of the unoperated vagus within its normal or ipsilateral wall of the GI tract. Although the regional patterns of the unoperated ipsilateral vagus were not affected, the packing densities of both types of afferents supplied by this trunk were moderately reduced. The DMNX of the vagotomized side displayed extensive (approximately 83%) neuronal loss; the DMNX on the unoperated side as well as the NST on both sides exhibited limited (approximately 20--25%) losses. The lack of a peripheral projection field reorganization -- except for a moderate down-regulation -- after complete unilateral denervation suggests that both the laterality and the afferent terminal phenotypes (or target tissues) of the vagus in the proximal GI tract are specified by postnatal day one in the rat. The present results, taken together with other observations, also suggest that three different combinations of signals orchestrate the commitments of vagal afferents respectively to (1) the side of the organ, (2) the region within the organ wall, and (3) the accessory and innervated tissues that complex with the fully differentiated ending.

Animals↗

PubMed2001

Metabolic and behavioral responses in pre-weanling rats following alteration of maternal diet.

In rat pups, blockade of fatty acid oxidation by administration of 2-mercaptoacetate (MA) produces an increase in independent ingestion by 12 days of age. In contrast, administration of methyl palmoxirate (MP) fails to increase intake or to alter oxidation of fatty acids in young rats due to the high proportion of medium chain triglycerides (MCT) in rat milk. In the present experiments, the composition of rat milk was altered by placing dams on a high fat (HF) diet to examine the development of ingestive responding in rat pups following administration of MP. Following delivery of MP (0.5--10 mg/kg), pups were placed in a cage inside an incubator for 1, 3, or 6 h, and then received an intake test consuming a commercial half-and-half milk diet from the floor of test containers. Blood was collected from additional groups of pups for measurement of beta-hydroxybutyrate (beta HBA) and glucose levels. The results demonstrated that administration of MP produced significant reductions in beta HBA levels after 3 h in 12- and 15-day-old pups, but behavioral responses were noted only in pups aged 15 days. Similar results were obtained following administration of MA to pups reared by dams on HF diets; physiological responses were observed at 12 and 15 days of age, but behavioral responses were not observed after administration of MA until 15 days of age. Taken together, these results suggest that (1) changes in fatty acid oxidation may represent an early metabolic signal that can influence intake in rat pups and (2) alteration of the dam's diet produces physiological and behavioral changes in the pups.

3-Hydroxybutyric Acid↗

PubMed2000

Effects of metabolic inhibitors on ingestive behavior and physiology in preweanling rat pups.

We have previously demonstrated that administration of 2-Mercaptoacetate (MA) stimulates independent intake after 1 h in 12 and 15-day-old rat pups, but not younger pups. MA also produces decreases in beta-HBA levels, consistent with the development of a role of altered fatty acid oxidation in modulating independent ingestion in rat pups by 12 days of age. The present experiments extended investigations of the role of changes in energy utilization in young rats by investigating the duration of the effects of altered fatty acid oxidation and the effects of combined blockade of fatty acid oxidation and glucose utilization. Pups were tested at 9, 12 or 15 days of age 3 or 6 h following administration of a dose of 0, 11.4, 22.8, 45.6 or 91.2 mg/kg MA. In pups aged 12 and 15 days, moderate doses of MA stimulated intake 3 h, but not 6 h, following administration. Administration of the highest dose of MA produced significant decreases in beta-HBA levels in pups at all ages when tested after 3 h, but not after 6 h. In the second set of experiments, behavioral and physiological responses to administration of MA (0, 11.4 or 22.8 mg/kg) combined with 2-Deoxyglucose (2-DG: 0, 100 or 200 mg/kg) were investigated in pups aged 6, 9, 12 or 15 days of age. The results demonstrated that while administration of 2-DG produced physiological responses, intake was not stimulated at any age by 2-DG alone or in combination with MA. In fact, in 12 and 15-day-old pups, administration of 2-DG blocked the stimulatory effects of administration of MA. Therefore, while altered utilization of glucose does not appear to be an effective stimulus for increased independent ingestion in pups at this age, altered fatty acid oxidation may be an early metabolic modulator of intake.

Age Factors↗

PubMed1999

Behavioral specificity of effects of 2-mercaptoacetate on independent ingestion in developing rats.

Blockade of fatty acid oxidation in rat pups using 2-Mercaptoacetate (MA) produces increases in independent ingestion by 12 days of age. In the present experiments, the behavioral specificity of the effects of MA on ingestion were examined. In the first experiment, administration of MA to pups aged 9 and 12 days of age failed to increase intake of an oral infusion of a milk diet. In the second experiment, administration of MA did enhance intake of a milk diet in a short-term test of consuming from the floor of a test container and the level of gastric fill appeared to determine intake during the test. Finally, administration of MA did not affect intake of water in 9- or 12-day-old pups. These results suggest that MA produces increases in intake through specific effects on selective ingestive responses and not through nonspecific behavioral arousal.

Animals↗

PubMed1998

Electromyographic analysis of oral habituation in rat pups.

Rat pups show decreases in mouthing activity in response to a series of repeated oral infusions of a diet. This decrease in mouthing activity has been termed "oral habituation" and these changes have been readily recorded with simple behavioral observations. Oral habituation appears to be a component of satiety in young rats. In the present study, to more specifically characterize changes in motor response topography during habituation in muscle groups used for mastication, mouthing activity was recorded by implanting fine wire electromyographic electrodes in the superficial masseter, anterior digastric, sternohyoideus, and genioglossus muscles of 12-day-old rat pups. During testing, pups received a series of brief oral infusions of a 10% sucrose diet delivered through an oral cannula. The results demonstrated that mouthing activity as observed and scored behaviorally was highly correlated with mouthing behavior recorded by EMG, with oral habituation distinctly emerging in both measures. In addition, the pattern of motor activity in the four masticatory muscles changed during the course of oral habituation. Within the minute following a single infusion, the cycle frequency, duration of activity, and relative onset time of activity in the four muscles changed. In addition, across the course of habituation, both cycle frequency and relative onset times of muscle activity changed. These results demonstrate the general reliability of behavioral observations of masticatory motor activity in young rats and provide further information on how the pattern of activity of muscles involved in the mouthing motor pattern is altered during the course of oral habituation.

Animals↗

PubMed1998

Habituation of oral responding in adult rats.

The effects of repeated oral stimulation on ingestive responding were investigated in adult rats. A series of brief intraoral infusions of flavored diet was delivered to female rats once every minute through an oral cannula. When the flavor of the infused diet remained constant, significant decreases in mouthing behavior were observed by the end of testing, whereas switching the flavor of the diet during testing resulted in enhanced responding and infusions delivered through gastric cannulas produced minimal effects. Patterns of oral responding were also similar in food-restricted rats. These patterns of responding suggest that adult rats habituate to oral stimulation. Finally, oral habituation led to decreased ingestion, whereas gastric infusions had minimal effects. Thus, oral habituation may represent a mechanism influencing intake in rats at all ages.

Animals↗

PubMed1997

Development of independent ingestive responding to blockade of fatty acid oxidation in rats.

The present studies examined the development of ingestive responsiveness to blockade of fatty acid oxidation in rat pups using 2-mercaptoacetate (MA), an inhibitor of mitochondrial acyl-coenzyme A dehydrogenases, or methyl palmoxirate (MP), an inhibitor of carnitine palmitoyltransferase I (CPT-I). Rat pups aged 6, 9, 12, or 15 days of age received an intraperitoneal injection of 0, 100, 200, 400, or 800 mumol/kg MA, and intake of a commercial half-and-half or 15% glucose diet from the floor of test containers was assessed in a 30-min test beginning 1 h after administration of MA. The results demonstrate that, although no dose of MA affected intake of either diet in pups 9 days or younger, low doses of MA increased intake and the highest dose suppressed intake of both diets in pups 12 days of age or older. Physiological measurements indicated that levels of beta-hydroxybutyrate were significantly lower following doses of 400 or 800 mumol/kg MA in 9-, 12-, and 15-day-old pups and that gastric emptying was inhibited in 12 and 15 day olds by 800 mumol/kg MA. Intake of a commercial half-and-half diet from the floor of test containers was also assessed in 12- to 18-day-old rat pups 6.5 h after they received a gavage load of 0, 1.25, 2.5, 5, or 10 mg/kg MP. Unlike MA, MP did not increase intake of a commercial half-and-half diet in rat pups 12 or 15-18 days of age; instead, the highest dose of MP suppressed intake in 15- to 18-day-old pups. The failure of MP to enhance intake in pups at the ages tested is likely related to composition of dam's milk; rat milk is high in medium-chain fatty acids that do not require CPT-I for entry into mitochondria. Thus it is likely that MP does not significantly block fatty acid oxidation in pups at the ages tested. On the other hand, blockade of fatty acid oxidation produced by MA significantly affects intake by 12 days of age, suggesting it may be the first metabolic signal that influences intake in rat pups.

3-Hydroxybutyric Acid↗

PubMed1996

Effects of oral experience on rewarding properties of oral stimulation.

The oropharyngeal sensory and motor experiences of ingestion have long been considered to be rewarding or motivating. Recent work has suggested that the reinforcing properties of oral stimulation are modulated by experience with an ingestive bout. Two processes that result from the repeated oral experience that occurs during an ingestive bout, sensitization and oral habituation, may influence the reinforcing or rewarding properties of oral stimulation. The first process, sensitization, describes an initial increase in responsiveness following the first presentation of a stimulus: such an increase in responding has been noted in the ingestive behavior of both rats and humans. The second process, oral habituation, occurs after sensitization of responding, and results from continued repeated exposure to oral stimulation. During oral habituation, ingestive responsiveness declines; decreased ingestive responding to oral stimulation is demonstrated even in the absence of substantial post-ingestive signals. Both oral habituation and sensitization reflect process through which experience may modulate the rewarding properties of oral stimulation.

Animals↗

PubMed1995

Effects of physiological state on oral habituation in developing rats: cellular and extracellular dehydration.

Hydrational state has been demonstrated to influence intake of various solutions in young rat pups. For instance, both cellular and extracellular dehydration produce an enhancement of intake in pups tested at 6 days of age. However, the behavioral mechanisms that result in increased intake following manipulations of hydrational state have been less extensively studied. The impact of hydrational state on behavioral responsiveness in young rat pups was examined by assessing the pattern of responding to a series of repeated oral infusions of diet. Pups were tested at 6, 12, or 18 days of age following either acute cellular dehydration produced by injection of 1 M NaCl or acute extracellular dehydration produced by injection of 10% polyethylene glycol (PEG). Oral responsiveness to a series of 30 brief infusions of one of four taste solutions (water, 10% sucrose, 0.135 M NaCl, or 1 M NaCl) was measured. Each infusion lasted 3 s and there was 1 min between infusions. The pattern of oral responding to solutions was affected by the developmental age of the pup, the hydrational state of the pup, and the solution offered, with the largest effects of dehydration observed in the youngest animals. In all conditions except one, pups habituated to repeated infusions. The exception was the failure of extracellularly dehydrated 6-day-old pups to display habituation to oral infusions of sucrose. These results suggest that, although intake is enhanced by both cellular and extracellular dehydration in very young pups, the behavioral changes responsible for the enhancement of intake after cellular dehydration are different from the behavioral changes resulting from extracellular dehydration. This dissociation of behavioral effects of dehydration in young pups demonstrates that intake measures alone may obscure subtle differences in behavior and argues for the utility of dissection of behavioral components in understanding the neural and physiological control of behavior.

Aging↗

PubMed1994

Does oral experience terminate ingestion?

Using data from studies of ingestive behavior in developing rat pups we demonstrate how oral experience can contribute to the termination of ingestion. In rat pups, repeated oral stimulation with sweet solutions causes a decline in oral responsiveness. The diminished responsiveness is specific to the flavor of the stimulus experienced orally and can persist for several hours. We suggest that this experience-based decrement in responsiveness is best considered "oral habituation" and that oral habituation largely accounts for the onset of satiety. Post-ingestive feedback signals may have their influence through the oral habituation process or act in the context of oral habituation. Oral habituation is also shown to depend on the pattern of stimulus presentation, a phenomenon that adds considerable complexity to assessing the contributions of oral experience to satiety. The concept of oral habituation may be useful in understanding the immediate control of ingestion and the moment-to-moment expression of ingestive behavior in adult animals.

Animals↗

PubMed1989

A nutritive control of independent ingestion in rat pups emerges by nine days of age.

The emergence of controls of independent ingestion in rat pups was studied using nutritive (0.6 M glucose in saline or water) and vehicle gastric preloads. Two hours after preloading, ingestive responses were assessed in a 30-minute test of feeding from the floor. In 6-day-olds, all preloads had similar effects on consumption of a milk diet. In 9-day-olds, however, glucose-water preloads inhibited intake compared to water preloads. This inhibition was secondary to an effect on gastric emptying. Glucose preloads also inhibited intake in 12- and 15-day-olds. Behavioral observations indicated that feeding patterns were altered in response to glucose preloads in 9-day-olds. These results provide evidence for the emergence of a nutritive, postgastric control of independent ingestion between 6 and 9 days of age.

Aging↗

PubMed1989

Open-field behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering.

The influence of the maternal environment on the development of open-field behavior in spontaneously hypertensive (SHR) rats was investigated using the technique of reciprocal cross-fostering. Entire litters of SHR and Wistar-Kyoto (WKY) normotensive rats were either reared by their natural mothers, in-fostered to dams of the same strain, or cross-fostered to dams of the opposite strain on the day after birth. Open-field behavior was assessed in male and female rats from the six groups (2 strains x 3 rearing conditions) at 30, 60, 90, and 120 days of age. Animals were observed in the open-field during a 5-min test period and the number of squares entered and hindlimb rears were recorded. At all ages tested, SHR rats were more active in the open field, entering more squares and rearing more frequently than WKYs. SHR females were more active than age-matched SHR males, while no sex differences were apparent in the WKY strain. At each age, open-field behavior was similar across WKY rearing groups. SHR control and in-fostered animals responded similarly in the open field; however, SHR cross-fostered rats (particularly females) tended to be more active than controls. Although cross-fostering has profound effects on cardiovascular development and functioning in the SHR, it appears that altering the early maternal environment experienced by SHR pups does not grossly affect the development of open-field behavior.

Animals↗

PubMed1988

Brain binding sites for atrial natriuretic factor (ANF): alterations in prehypertensive Dahl salt-sensitive (S/JR) rats.

The binding of radioiodinated atrial natriuretic factor (125I-ANF-28) to discrete areas of brain in 7 week old, inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats was studied utilizing quantitative film autoradiography. At this age, S/JR rats exhibit systolic blood pressures that are prehypertensive and tend to be slightly higher than systolic blood pressures of age-matched R/JR rats. Scatchard analysis of 125I-ANF-28 binding in forebrain revealed that S/JR rats have a significantly increased number of binding sites for 125I-ANF-28 in the subfornical organ as compared to R/JR controls. In contrast, values for 125I-ANF-28 binding capacity in the choroid plexus and area postrema were similar for both strains, and binding affinity constants for 125I-ANF-28 binding revealed no strain differences in any brain area examined. The elevation in the number of binding sites for atrial natriuretic factor may serve as a compensatory mechanism acting in part to lower fluid volume and sodium levels prior to the precipitous increase in blood pressure which occurs in S/JR rats by 10 weeks of age.

Animals↗

PubMed1988

ANF receptors: distribution and regulation in central and peripheral tissues.

Atrial natriuretic factor is a recently-discovered family of biologically active peptides produced in, stored and secreted by mammalian atria. ANF exerts a wide variety of actions in the periphery as well as within the central nervous system. In general, these actions are directed toward the maintenance of body fluid and electrolyte balance and regulation of arterial blood pressure. In a fashion similar to that of many other hormonal systems, the actions of ANF in various target tissues appear to be mediated by at least one class of specific receptors. However, while the biosynthesis and biological actions of ANF have been extensively investigated, little research has been focused on ANF receptor systems. In this article, we will provide an overview of current literature regarding the distribution and binding characteristics of receptor sites for ANF in peripheral and central target tissues. In addition, we will consider factors involved in the regulation and alteration of ANF receptor sites in various tissues. Finally, a brief discussion of the emerging concept of ANF and angiotensin II as mutual antagonists in body fluid homeostasis and cardiovascular regulation will be offered.

Animals↗

PubMed1987

Binding sites for atrial natriuretic factor (ANF) in kidneys and adrenal glands of spontaneously hypertensive (SHR) rats.

Binding sites for atrial natriuretic factor (ANF) were studied in kidneys and adrenal glands of 17 week old male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats by quantitative autoradiography using 125I-ANF-28. In kidney, 125I-ANF-28 binding sites were found in high concentrations in glomeruli and in much lower concentrations in the renal papilla. In adrenal gland, 125I-ANF-28 binding sites were highly localized to the zona glomerulosa and were of moderate density in the inner cortical regions. ANF binding sites did not occur in the adrenal medulla. The maximum binding capacity (Bmax) of 125I-ANF-28 was reduced by 50% in the kidney glomeruli of SHRs compared to WKY controls. In contrast, the affinity constant (Ka) for 125I-ANF-28 was elevated by 100% in kidney glomeruli of SHRs. There were no significant strain differences in values for Bmax or Ka for 125I-ANF-28 binding in the adrenal zona glomerulosa. These findings suggest that the natriuretic and diuretic actions of ANF within kidney glomeruli may be compromised in adult SHR rats and these alterations may contribute to the development and maintenance of hypertension in rats of this strain.

Adrenal Cortex↗

PubMed1987

Alterations in binding sites for atrial natriuretic factor in kidneys and adrenal glands of Dahl hypertension-sensitive rats.

Binding sites for atrial natriuretic factor (ANF) were studied in kidneys and adrenal glands of 7- and 10-week-old male Dahl hypertension-sensitive (S/JR) and hypertension-resistant (R/JR) rats by quantitative autoradiography. Binding sites for 125I-ANF-28 in kidney were highly localized and of high density in the glomeruli; binding sites were less concentrated in the renal papilla. In adrenal gland, binding sites for 125I-ANF-28 were highly concentrated in the zona glomerulosa, but were of a very low density in the inner adrenal cortex. At 7 weeks of age, the maximum binding capacity (Bmax) for 125I-ANF-28 in kidney glomeruli was increased by 21% in S/JR rats compared with R/JR rats. From 7 to 10 weeks of age, decreases in Bmax for 125I-ANF-28 in glomeruli occurred, with no apparent difference between strains. Strain or age differences in the affinity constant (Ka) for 125I-ANF did not occur in the kidney. In adrenal zona glomerulosa, the Bmax for 125I-ANF-28 binding was similar for S/JR and R/JR rats at 7 weeks of age. At 10 weeks of age, however, Bmax for 125I-ANF-28 in adrenal zona glomerulosa was increased by 19% in S/JR rats compared with age-matched R/JR controls. These findings suggest that alterations may occur in ANF binding sites in kidney and adrenal gland of S/JR rats in response to the sharp increase in blood pressure that is characteristic of rats of this strain.

Adrenal Cortex↗