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Biomedical subjects

M A Hofer

Publications and source records attributed to M A Hofer.

At least 55 records · Page 3Linked to original sources

Trigeminal and olfactory pathways mediating isolation distress and companion comfort responses in rat pups.

Isolation in a novel test cage elicits ultrasonic vocalization (USV) in 12-13-day-old rat pups, and the presence of an anesthetized littermate companion reduces USV while eliciting body contact. These responses were studied in pups with surgical lesions of trigeminal snout afferents and after olfactory denervation by nasal ZnSO4 perfusion. With lesions of only one system, body contact with the passive companion was reduced by 20%, and interpup orientation was differentially affected by the two types of lesions. However, USV rates were no different from littermate controls in the presence of the companion or when tested alone. Combined lesions of both systems reduced contact time 55% and eliminated any reduction in USV rates by the companion while leaving intact USV and locomotor responses to isolation. These results suggest that different sensory pathways may mediate isolation distress and companion comfort responses.

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The effects of opioid and benzodiazepine antagonists on dam-induced reductions in rat pup isolation distress.

In 10-day-old pups isolated in a novel environment, the presence of the dam reduced the rate of ultrasonic vocalization by 93%. The opiate antagonist naltrexone caused a dose-related increase in the rate of vocalization that was significant only at 5.0 mg/kg. This suggests that the dam exerts comforting effects through endogenous opioid mechanisms. Although the benzodiazepine agonist chlordiazepoxide is as effective as morphine in the quieting of isolation distress, its antagonist, Ro 15-1788, at doses up to 20 mg/kg did not alter the lowered rate of vocalization associated with the presence of the dam. Instead, it facilitated quiet contact with the companion. This raises the possibility that the presence of a social companion precludes the release of an endogenous anxiogen that binds to the benzodiazepine receptor.

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Independence of benzodiazepine and opiate action in the suppression of isolation distress in rat pups.

To determine whether benzodiazepines (BDZs) quiet isolation distress in 10-day-old rat pups by causing a release of endogenous opioids, a blockade of the effects of chlordiazepoxide (CDP) by the opiate antagonist naltrexone (NLX) was sought. Nonsedating doses of morphine (MOR) (0.125 mg/kg) and CDP (2.0 mg/kg) were equally effective in reducing ultrasonic vocalizations and other indices of isolation distress. Appropriate blocking agents NLX, (0.5 mg/kg) against MOR and Ro 15-1788 (4.0 mg/kg) against CDP returned distress measures to levels of saline-treated rat pups. However, NLX failed to reverse the quieting effects of CDP. If CDP potentiates endogenous opioid release, then NLX should block the CDP effect. A higher dose of CDP did not reveal a release of endogenous opioids, and a higher dose of NLX did not antagonize CDP. The quieting effects of BDZs on isolation distress do not appear to be mediated by the opiate system.

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Socially mediated reduction of isolation distress in rat pups is blocked by naltrexone but not by Ro 15-1788.

The presence of a single anesthetized littermate significantly reduced the rate of ultrasonic vocalization by 10-day-old pups isolated in a novel environment. Naltrexone (1.0 mg/kg) returned the vocalization rate to the level of pups tested alone and disrupted the maintenance of body contact between the test pup and a companion. This suggests that the companion exerts comforting effects through endogenous opioid mechanisms. Although chlordiazepoxide is as effective as morphine in the quieting of isolation distress, the benzodiazepine (BDZ) antagonist Ro 15-1788 (5, 10, or 20 mg/kg) was ineffective in blocking the comfort effect and facilitated quiet contact with the companion. In isolated pups, Ro 15-1788 caused a significant, but not a dose-related, decrease in vocalization, a possible indication of the displacement of an endogenous anxiogenic ligand at the BDZ receptor complex.

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Maternal behavior of SHR rats and its relationship to offspring blood pressures.

In Part I of this study maternal behavior of 15 spontaneously hypertensive (SHR) and 11 Wistar-Kyoto (WKY) rat mothers was recorded throughout the preweaning period. SHR mothers were observed: 1) in arched-and blanket-nursing postures more often, and in passive-nursing posture less often, 2) licking their pups more often, and 3) resting less often. Further, SHR mothers retrieved their pups more quickly than did WKY. In the second part of this study we found that a composite maternal behavior score, derived from summing occurrences of mother/pup contact, arched-nursing, and pup-licking, was positively correlated with the offspring blood pressures. This relationship, which accounted for 43.5% of the variance in adult blood pressure, suggests that certain types of interactions between mothers and their pups may contribute to individual differences in cardiovascular system development.

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Relationships between maternal behavior of SHR and WKY dams and adult blood pressures of cross-fostered F1 pups.

In this experiment SHR and WKY dams reared genetically identical F1 pups derived from SHR x WKY matings. We found that a composite maternal behavior score was positively correlated with adult blood pressures of the fostered offspring. This replicated a similar finding from our previous study in which SHR and WKY mothers reared their own pups. Unlike this previous study, WKY dams rearing F1 pups exhibited maternal behavior patterns similar to SHR dams. Finally, we found there was no effect of the strain of foster mother upon adult blood pressures of the F1 offspring. These results indicate that some aspects of maternal behavior may change as a function of pup characteristics, and support our hypothesis that the cardiovascular system may be shaped by experiences of early life which are embedded in mother/young behavioral interactions.

Age Factors↗

Early experience and maternal behavior in rats.

This study examined the effects of early experience (early weaning with group housing in sibling groups (EG), or early weaning plus social isolation (EI) from 14 to 24 days of age) on maternal, play, and social behaviors expressed during 5 days of sensitization at 24 days, and then later at 100 days of age. Our results showed that maternal behaviors at 24 days could be altered by these early experiences. At 24 days of age fewer EI animals retrieved compared with normally weaned controls (NW), but more showed play behavior in the presence of pups. EG animals showed intermediate levels of retrieving relative to NW controls, and no concomitant changes in play behaviors. When retested as adults, females in all groups showed similar levels of all maternal behaviors. But EI adults of both sexes showed persistent intrusion of play behaviors, and higher levels of rearing and undirected activity in the presence of neonates. Factor analyses revealed that previously sensitized adult males showed patterns of organization of maternal behaviors that resembled adult females rather than those shown by control males reared without sensitization experience. Previously sensitized females also showed a retention of the play behavior patterns characteristic of juveniles, not present in females without sensitization experience. These results show that social experience during the weaning period can affect the development of maternal and play behavior elicited by neonates during the juvenile period that persist into adulthood, and the juvenile sensitization experience exerts longterm effects on adult patterns of maternal behavior in both sexes.

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Nursing interaction of Wistar rats is modified by prior experience of altered nursing bout length.

We tested the capacity of 2 week postpartum Wistar rat litters and their dams to adapt to experimental shortening and lengthening of the time available for nursing while maintaining the frequency of bouts constant, using manual transfer between cage compartments. In 8-hr and 24-hr experiments, the short bout group (10 min/hr) gradually came to show normal litter weight gain, short latency milk ejections, and increased high arched nursing position, while the 40-min/hr group showed increased latency to attachment and longer latency to ME compared to the 20 min/hr control group. Pup body temperature did not vary between groups. Although pups in the 10-min group showed increased dam-directed behaviors in the first 8h, this difference vanished thereafter. In a twenty-fifth cycle, after dams and litters were exchanged, the prior experiences of the dams and not of the litters were found to determine the dynamics of milk exchange.

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Isolation distress and maternal comfort responses of two-week-old rat pups reared in social isolation.

In 2-week-old rats, isolation from social companions in an unfamiliar place elicits ultrasonic vocalization rearing and locomotor behavior. These responses are prevented and close body contact is maintained if littermates or the dam are present. It has generally been believed that such isolation distress and comfort responses develop as a result of prior social experience. We reared pups in isolation from the third postnatal day and found essentially normal responses. A second experiment replicated and extended these results to pups reared in isolation from the day of birth. Isolation-reared pups did have higher levels of ultrasonic vocalization than their normally reared littermates, lower body weight, and lower post-test temperatures. We conclude that a lengthy period of close body contact and frequent social interactions with conspecifics are not necessary for the development of attachment responses in this species.

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Baroreceptor sensitivity in two-week-old rat pups: effects of nutrient deprivation and sino-aortic denervation.

Resting cardiac rates are reduced 40% by nutrient deprivation in two-week-old rats while arterial pressure is maintained at stable levels. Previous evidence implicated arterial baroreceptors and suggested the hypothesis that the cardiac rate changes result from increased baroreceptor sensitivity following nutrient deprivation. In order to test this hypothesis, cardiac reflex responses were elicited by graded doses of phenylephrine and sodium nitroprusside before and after nutrient deprivation. Although cardiac rate decelerations in response to phenylephrine were greater in fed pups (p less than 0.05) and acceleration in response to nitroprusside were greater in the deprived condition (p less than 0.01), these could be attributed to 'ceiling' and 'floor' effects of the resting cardiac rates characteristic of the two nutrient conditions. Sino-aortic denervation eliminated cardiac reflex responses, substantiating their dependence on baroreceptor afferents. Regression analysis of cardiac reflex responses to arterial pressure changes failed to show changes in baroreceptor sensitivity that would support the hypothesis. Alternate mechanisms mediating the nutrient effect on cardiac rate (e.g., involving neural and peptide hormonal pathways) should be pursued.

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Premature maternal separation and lymphocyte function.

Premature separation of rat pups from their mothers, on postnatal Day 15, produced a decreased response of peripheral blood lymphocytes to phytohemagglutinin (PHA) at 40 days of age. A significant lymphopenia was also found in the early weaned animals at 40 days of age although this was accounted for statistically by their lower body weight. These consequences of early maternal separation may have been mediated through the effects of early separation on nutritional state, hypothalamic function, or maturation of the immune system.

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Isolation distress in two-week-old rats: influence of home cage, social companions, and prior experience with littermates.

Behavioral and autonomic manifestations of acute isolation distress were studied in 2-week-old rats under novel and home-cage conditions. Levels of ultrasonic vocalization, heart rate, self-grooming, and rises were higher in novel surroundings, while locomotion and digging were more frequent in home cages. Next, we found that a group of 8 unanesthetized agemate pups was just as effective as an anesthetized dam in reducing (by 80-90%) all behaviors of isolated pups in novel surroundings. Finally, singletons reared without littermates during postnatal days 7-14 showed normal isolation responses, and these were as effectively alleviated by littermates as those of normally reared pups. Thus, isolation distress in rats this age is a complex response, modulated over time by aspects of the pups' environment and virtually prevented by the presence of cues common to both mother and littermates.

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Behavioral responses of juvenile rats (Rattus norvegicus) to neonates after infusion of maternal blood plasma.

Individual 18- or 30-day-old male and female Wistar rats (juveniles) were continuously exposed to 3-8-day-old pups for 5 days (sensitization) after intravenous (iv) infusion of maternal blood plasma (PL group) or 5% dextrose and water (IC group) through chronically implanted cannulas and were compared with nonhandled littermate controls (NHC group). The results showed complex interactions with sex and age of the animals tested, depending upon which maternal behaviors were examined. First, plasma from parturient females selectively increased retrieving behavior in 30-day-olds, and it was more powerful in females than in males. Second, on the first day, prior to sensitization, both PL and IC 30-day-olds showed higher frequencies of retrieving, crouching, anogenital licking, and contact than did nonhandled juveniles. Third, 30-day-olds that received maternal blood plasma continued to retrieve pups, with a latency peak for retrieving occurring at 72 hours, suggesting a long-term effect of plasma not seen in control animals. Fourth, 18-day-old subjects did not generally show effects of any of our manipulations, but they did show more nest building and contact behaviors than did 30-day-old subjects. Last, we found that the iv cannulation and infusion procedures led to a persistent dissociation of retrieving behavior from play in older animals and an integration of retrieving with crouching and licking regardless of whether maternal plasma or control infusion was administered. Retrieving behavior was associated with play behaviors (charge and pounce) in younger juveniles and in older, nonhandled control animals irrespective of treatment. For these animals, no integration of retrieving occurred with other maternal behaviors.

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Early social relationships: a psychobiologist's view.

This article outlines a strategy for studying early social relationships in relatively simple animal model systems. It describes some of the differences in approach between neuroscientists and human developmentalists in dealing with the same research problems. These ideas are then illustrated in work from our laboratory on the processes of early social attachment in young rats and on their responses to separation from their mothers. We have found evidence for a novel mechanism by which the mother appears to be a regulator of physiological and behavioral systems of the infant so that many of the prolonged responses to separation represent withdrawal or release phenomena. Finally, I will describe some surprising results from our studies on the organization of nursing that reveal an unexpected degree of synchrony and reciprocity in this apparently simple interaction that is so basic to being a mammal.

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Olfactory-guided orientation in neonatal rats is enhanced by a conditioned change in behavioral state.

In Experiment 1, 3-6-day-old rats were simultaneously exposed to an unfamiliar odor which they will normally avoid (orange extract) and the odor of maternal saliva, or to either orange alone or saliva alone. One hour later, in a two-odor choice test, those pups which were simultaneously exposed to orange and saliva exhibited an enhanced orientation to the orange odor. In Experiment 2, orange odor was presented while pups were exposed to the odor of saliva, or while they received one of two types of tactile stimulation (stroking or tailpinching). Pups in control groups were first presented with saliva or tactile stimulation and then the orange odor. Pups that had received any of the three simultaneous exposure treatments subsequently exhibited an enhanced orientation toward the orange odor, but not the pups in the control groups. The results suggest that the tendency of neonates to avoid a novel odor can be reversed by pairing that odor with events that elicit significant increases in behavioral activity. The possibility that this phenomenon reflects a classical conditioning process is discussed.

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Huddling and independent feeding of neonatal rats can be facilitated by a conditioned change in behavioral state.

Infant rat pups were exposed to a novel odor (orange or cedar) while they received tactile stimulation (stroking of the body) or were presented with odor or stroking alone. The effects of these treatments were assessed on pups' performance in a huddling test (Experiment 1 and 2) and an independent feeding test (Experiment 3). During these tests, only pups that had received the simultaneous presentation of the odor and stroking exhibited an increase in huddling and feeding. The increase in these behaviors was dependent on the presence of the conditioned odor during testing.

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Nutrient control of cardiac rate in the infant rat: alpha-adrenergic mechanisms.

Changes in level of nutrient intake have been shown to exert a major influence on beta-adrenergic cardiac activity in 2 week old suckling rats. A series of experiments demonstrates that the alpha-adrenergic vasoconstrictor system is functional by 2 weeks postnatal age, and that alpha-adrenergic blockade with phenoxybenzomine (PBZ) does not affect the high heart rates of well-fed pups but prevents development of the bradycardia after cessation of suckling and fully reverses the low heart rates of nutrient-deprived pups in a dose-dependent manner. This last effect is dependent upon beta-adrenergic reflex cardiac pathways. After PBZ, milk feeding no longer produces cardiac acceleration in nutrient-deprived pups. Systolic and mean arterial pressure during PBZ administration and estimates of plasma volume change during nutrient deprivation are consistent with the inference that changes in peripheral resistance, mediated by the alpha-adrenergic vasoconstrictor system, accompany nutrient regulation of cardiac rate in the suckling rat.

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Blood pressure responses to milk ejection in the young rat.

When young rats receive milk ejections from their mothers they exhibit abrupt 30-50% increases in blood pressure. In our first experiment, we recorded, via carotid cannulae, blood pressure and heart rate during natural nursing bouts. Blood pressure changes coincident with behaviorally defined milk ejections were twice as large as the changes associated with other behaviors observed. In addition, the increases in blood pressure during milk ejection were significantly greater when pups were separated from their mothers for 18-20 hours prior to testing. A second experiment showed that these responses were independent of the mother's overt behavior because virtually identical results were obtained when pups received milk from anesthetized dams stimulated to release milk with oxytocin. These results are discussed with regard to possible immediate functions of the response, and long term effects of repeated cardiovascular activation in early development.

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