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Biomedical subjects

G Sokoloff

Publications and source records attributed to G Sokoloff.

15 recordsLinked to original sources

Competition and cooperation among huddling infant rats.

Huddling is expressed by infant rats and continues to be an important behavior throughout adulthood. As a form of behavioral thermoregulation, huddling is thought to play an essential role in compensating for inadequate physiological thermoregulation early in development. Infant rats, however, are capable of heat production shortly after birth using brown adipose tissue (BAT) and exhibit thermogenesis in the huddle, suggesting that huddling does not obviate the need for endothermy during cold exposure. In the present experiment, 4-pup huddles of infant rats (2- or 8-day-olds) were exposed to two subthermoneutral temperatures, and BAT thermogenesis was inhibited in 0, 2, or 4 of the rats in each huddle. Inhibition of BAT thermogenesis compromised the pups' ability to maintain huddle temperature, but surprisingly did not result in enhanced huddling at either age. These results suggest that effective huddling during cold exposure requires the thermal resources provided by endothermy. Furthermore, the heat provided by BAT appears to shape behavioral interactions in the huddle during development.

Animals↗

Do infant rats cry?

In the current revival of interest in the emotional and mental lives of animals, many investigators have focused attention on mammalian infants that emit distress vocalizations when separated from the home environment. Perhaps the most intensively studied distress vocalization is the ultrasonic vocalization of infant rats. Since its discovery, this vocalization has been interpreted both as a communicatory signal for the elicitation of maternal retrieval and as the manifestation of emotional distress. In contrast, the authors examined the cardiovascular causes and consequences of the vocalization, and on the basis of this work, they hypothesized that the vocalization is the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that results in increased venous return to the heart. Therefore, the vocalization may be analogous to a sneeze, serving a physiological function while incidentally producing sound.

Adrenergic alpha-Agonists↗

A comparative analysis of huddling in infant Norway rats and Syrian golden hamsters: does endothermy modulate behavior?

In infant rats, huddling improves surface-to-volume ratios and provides metabolic savings during cold exposure. It is unclear, however, whether endothermy is also a necessary component of huddling. In the present experiment, huddles composed of infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian golden hamsters (8-day-olds), which do not produce heat endogenously, were exposed to decreases in air temperature. Behavioral and physiological responses were monitored throughout the test. Rats, especially at 8 days of age, were better able to thermoregulate using huddling than hamsters, due in part to endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral responses that promote heat retention, suggesting that both physiological and behavioral mechanisms contribute to effective thermoregulation during huddling in the cold.

Adipose Tissue, Brown↗

Distress vocalizations in infant rats: what's all the fuss about?

Ultrasonic vocalizations emitted by infant rodents are typically characterized as cries of distress. There are two contexts that are known to reliably elicit ultrasound production: extreme cold exposure and administration of clonidine, an alpha 2 adrenoceptor agonist. Noting that these two contexts both entail pronounced decreases in cardiac rate, we have hypothesized that the vocalizations are acoustic by-products of a physiological maneuver, the abdominal compression reaction (ACR), that increases venous return to the heart when return is compromised. As a critical test of this hypothesis, we measured venous pressure near the right atrium in 15-day-old rats after clonidine administration. Consistent with the ACR hypothesis, emission of ultrasound was accompanied by large and reliable increases in venous pressure and, therefore, venous return. These results provide strong, direct support for the ACR hypothesis and, by doing so, underscore the potential pitfalls of anthropomorphic interpretations of the vocalizations of infant rats.

Abdomen↗

A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.

Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.

Animals↗

Cardiovascular mediation of clonidine-induced ultrasound production in infant rats.

In infant rats, administration of the alpha2 adrenoceptor agonist clonidine simultaneously evokes ultrasound production and bradycardia. In this study the authors examined in 8-day-old rats whether these 2 responses to clonidine are causally related. In Experiment 1 pups were pretreated with saline or prenalterol (0.1 or 1.0 mg/kg), a beta1 adrenoceptor agonist that increases cardiac rate, followed by administration of clonidine (1.0 mg/kg). Prenalterol pretreatment suppressed clonidine-induced ultrasound production at both doses. Prenalterol also increased skin temperature, however, suggesting that suppression of ultrasound was modulated in part by increased body temperature. Consistent with this suggestion, in Experiment 2 mild hyperthermia significantly inhibited clonidine-induced ultrasound production. Finally, in Experiment 3 the authors found that the pretreatments used in Experiments 1 and 2 prevent or dampen the effects of clonidine on cardiac rate. These results suggest that clonidine's effect on ultrasound production is mediated by its effects on the cardiovascular system.

Adrenergic alpha-Agonists↗

Cardiovascular concomitants of ultrasound production during cold exposure in infant rats.

Two experiments explored the cardiovascular consequences of extreme cold exposure and their relationship with ultrasound production in infant rats. Experiment 1 addressed the thermoregulatory and cardiovascular concomitants of ultrasound production during cold exposure in rats pretreated with saline or the ganglionic blocker chlorisondamine (5 mg/kg). For both groups, emission of ultrasound was associated with hypothermia and bradycardia. Experiment 2 explored whether the hypothermia experienced by pups in Experiment 1 is associated with increased blood viscosity, which is an important factor affecting venous return to the heart. Blood viscosity increased significantly as temperature decreased from 38 degrees C to 22 degrees C. These experiments suggest that, during extreme cold exposure, decreased cardiac output and increased blood viscosity combine to diminish venous return. The authors have hypothesized that pups respond to decreased return by recruiting the abdominal compression reaction, a physiological maneuver that propels blood back to the heart, resulting in emission of ultrasound as an acoustic by-product.

Animals↗

Thermoregulatory and cardiac responses of infant spontaneously hypertensive and Wistar-Kyoto rats to cold exposure.

Cardiovascular function during cold exposure is dependent on effective thermoregulation. This dependence is particularly apparent in infants. For example, we have previously demonstrated that in infant rats during cold exposure, cardiac rate is directly related to their ability to produce heat endogenously. The primary source of endogenous heat production for infant rats is brown adipose tissue (BAT). Because of the dependence of cardiac rate on effective thermoregulation in the cold and because hypertension in spontaneously hypertensive rats (SHR) is influenced by the preweanling environment, in this study we examined the thermoregulatory and cardiac rate responses of infant SHR and Wistar-Kyoto rats (WKY) to varying levels of cold exposure. In experiment 1, 7- to 8-day-old SHR and WKY were acclimated at a thermoneutral air temperature (35 degrees C) and then exposed to successive decreases in ambient temperature (30.5 degrees C, 26.5 degrees C, 23 degrees C, and 17 degrees C) while thermal and metabolic measures were recorded. Although both strains increased BAT thermogenesis and oxygen consumption in response to cold exposure, SHR cooled more than WKY and exhibited lower levels of oxygen consumption at the lowest air temperatures. Experiment 2 was identical to experiment 1 except that cardiac rate was also measured. Again, SHR exhibited substantial thermoregulatory deficits compared with WKY; in addition, they were less able than WKY to maintain cardiac rate at the 2 lowest air temperatures tested. Finally, in experiment 3, infant SHR exhibited diminished BAT thermogenesis in response to a range of doses of a selective beta3-adrenoceptor agonist. We hypothesize that long-term thermoregulatory deficits during the early postnatal period influence cardiovascular function and contribute to the development of hypertension in SHR.

Acclimatization↗

Thermoregulatory competence and behavioral expression in the young of altricial species--revisited.

The behavioral and physiological thermoregulatory capabilities of newborn and infant mammals have been studied for over half a century. Psychobiologists have noted that the infants of altricial species (e.g., rats) have physical and physiological limitations such that heat loss overwhelms heat production, thus forcing a reliance on behavioral thermoregulation for the maintenance of body temperature. Recent evidence, however, suggests that a modification of this view is justified. Specifically, throughout a range of moderately cold air temperatures, nonshivering thermogenesis by brown adipose tissue contributes significantly to the infant rat's behavioral and physiological adaptations to cold challenge. Given the prominent use of altricial species for the study of infant behavior, increased understanding of the infant's physiological responses to cold and the effect of thermal factors on behavior is warranted.

Adaptation, Physiological↗

Active sleep in cold-exposed infant Norway rats and Syrian golden hamsters: the role of brown adipose tissue thermogenesis.

It was previously hypothesized that brown adipose tissue (BAT) thermogenesis helps to maintain high rates of myoclonic twitching during cold exposure in infant rats (M. S. Blumberg & M. A. Stolba, 1996). To test this hypothesis, the sensitivity of twitching to various levels of cold exposure was assessed in week-old rats that were untreated or whose BAT thermogenesis was inhibited using a ganglionic blocker. Because week-old golden hamsters do not exhibit BAT thermogenesis, their sleep behaviors during cold exposure also were examined. Additional investigations in infant rats were conducted in which supplemental heat was provided to the interscapular region using a thermode and in which BAT was activated pharmacologically in ganglionically blocked pups. The results support the hypothesis that myoclonic twitching is sensitive to the prevailing air temperature and the activation of BAT thermogenesis.

Adipose Tissue, Brown↗

Further evidence that BAT thermogenesis modulates cardiac rate in infant rats.

Previous research in infant rats suggested that brown adipose tissue (BAT), by providing warm blood to the heart during moderate cold exposure, protects cardiac rate. This protective role for BAT thermogenesis was examined further in the present study. In experiment 1, 1-wk-old rats in a warm environment were pretreated with saline or chlorisondamine (a ganglionic blocker), and then BAT thermogenesis was stimulated by injection with the beta3-agonist CL-316243. In experiment 2, pups were pretreated with chlorisondamine and injected with CL-316243, and after BAT thermogenesis was stimulated the interscapular region of the pups was cooled externally with a thermode. In both experiments, cardiac rate, oxygen consumption, and physiological temperatures were monitored. Activation of BAT thermogenesis substantially increased cardiac rate in saline- and chlorisondamine-treated pups, and focal cooling of the interscapular region was sufficient to lower cardiac rate. The results of these studies support the hypothesis that BAT thermogenesis contributes directly to the modulation of cardiac rate.

Adipose Tissue, Brown↗

Thermogenic, respiratory, and ultrasonic responses of week-old rats across the transition from moderate to extreme cold exposure.

Previously, it was reported that week-old rats exposed to air temperatures that elicited submaximal levels of heat production (designated moderate cold exposure) remained asleep and did not vocalize (Blumberg & Stolba, 1996). In contrast, pups exposed to air temperatures that elicited maximal levels of heat production (designated extreme cold exposure) woke up and emitted ultrasonic vocalizations. We now report on the physiological and behavioral responses of pups in the transitional region between moderate and extreme air temperatures. Small decreases in air temperature across the transition resulted in pronounced decreases in physiological temperature and concomitant increases in ultrasound production. In a second experiment, it was shown that during moderate cold exposure respiratory frequency increased as air temperature decreased but, as extreme air temperatures were reached, respiratory frequency was maximized as ultrasound production began. The results from these two experiments illustrate how air temperatures that differ by as little as 2 degrees C can differentially modify the physiological and behavioral responses of neonates.

Animals↗

Brown fat thermogenesis and cardiac rate regulation during cold challenge in infant rats.

Infants rats depend on heat production by brown adipose tissue (BAT) during cold challenge. Although it has been suggested that BAT thermogenesis protects the heart in the cold, the relationship of BAT activation to cardiac rate has not been examined directly. In the first experiment, the cardiac rate of 2- and 7- to 8-day-old rat pups was monitored during moderate and extreme cold challenge. Pups at both ages maintained cardiac rate during moderate cold challenge while BAT thermogenesis was increasing. In contrast, cooling to air temperatures at which BAT thermogenesis could increase no further resulted in pronounced bradycardia. In the second experiment, ganglionic blockade was used to eliminate BAT heat production and autonomic control of the heart in 7- to 8-day olds. Blockade suppressed BAT thermogenesis in the cold and led to pronounced decreases in interscapular temperature and cardiac rate. These data suggest that cardiac rate in infant rats is modulated both by the autonomic nervous system and BAT thermogenesis.

Acclimatization↗

Pontine and basal forebrain transections disinhibit brown fat thermogenesis in neonatal rats.

Bignall, Heggeness and Palmer (1975) were the first to demonstrate increases in metabolic heat production following midpontine transection in neonatal rats. Subsequent work in adult rats has shown that this procedure disinhibits thermogenesis by brown adipose tissue (BAT). Bignall and his colleagues also found that hypothalamic ablation did not result in increased thermogenesis in 5-day-olds, leading them to conclude that thermoregulation depends on more caudal structures at that age. We have also found that midpontine transection disinhibits BAT thermogenesis and, furthermore, have extended that finding to newborn pups. When transections were made in the basal forebrain, however, we also found profound and rapid increases in brown fat thermogenesis. These results suggest the presence of at least two sources of inhibition of BAT thermogenesis in newborn rats: one located in the rostral pons-caudal midbrain and one located in the basal forebrain.

Adipose Tissue↗

Dynamics of brown fat thermogenesis in week-old rats: evidence of relative stability during moderate cold exposure.

Neonates of many mammalian species, including humans, depend primarily on thermogenesis by brown adipose tissue as a defense against cold challenge. Although the steady-state thermogenic responses of brown adipose tissue to various air temperatures are well known, the dynamic responses have received relatively little attention. In this article, we examine the relative stability of brown adipose tissue thermogenesis during brief perturbations of air temperature. Specifically, week-old rats were allowed to settle at one of two levels of cold exposure. These two levels were defined on the basis of previous work as being moderate (30.5 degrees C) or extreme (23 degrees C). After pups had settled at these temperatures, they were exposed to positive or negative air temperature perturbations of approximately 3.7 degrees C. Pups experiencing perturbations from the moderate air temperature, unlike those exposed to the extreme air temperature, exhibited organized thermogenic responses that allowed them to return quickly to their preperturbation conditions. These data suggest that brown adipose tissue thermogenesis is more stably controlled than has previously been suspected.

Adipose Tissue, Brown↗