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Biomedical subjects

S E Swithers

Publications and source records attributed to S E Swithers.

12 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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