Biomedical subjects
Publications and source records attributed to M A Hofer.
Milk fed by stomach tube to 2-week-old rats separated from their mothers without feeding for 16 hours transiently but fully reversed the decrease in cardiac rate which had occurred during separation. This effect was rapid in onset and was related to dosage; it was not dependent upon gastric distention, but did depend upon beta-adrenergic transmission.
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Decreases of 40 percent in cardiac and respiratory rates occur during the first 12 to 16 hours after 2-week-old rat pups are separated from their mothers. These rates decrease without significant alteration in activity level and despite maintenance of body temperature, of nutrition by intubation, of an intact litter, and of the home cage nest.
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Twelve-day-old isolated rat pups reduce their rates of ultrasonic vocalization (USV) when an anesthetized adult is placed into the test cage, whether the adult is their dam or an unfamiliar male. USV rates remain very low even after removal of the male (inhibition). However, after removal of the dam, pups greatly increase their rates of USV over their first isolation period (potentiation). USV potentiation can be induced by either an awake, normally behaving dam or by one that is anesthetized. To test the role of olfaction in inhibition and potentiation, PND12 pups were rendered anosmic via intranasal infusion of 5% zinc sulphate (ZnSO4). Control pups were infused with normal saline. After overnight separation from the dam, the USV and other behaviors of pups were recorded during a 6-min test. Each pup was tested during an initial isolation period and a final isolation period. In the first experiment, an anesthetized adult (dam or unfamiliar male) or no companion was placed in contact with the pup during the middle minute. Anosmia prevented both potentiation and inhibition of USV by passive adult contact. Thus, it seems likely that pups use olfactory discrimination as the basis for these two highly differentiated vocal responses to social stimuli. Results from two additional experiments demonstrate that anosmia does not prevent potentiation when the adult dam is active and interacting with the pup on either postnatal day 12 or 8.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Series of analytic experiments are presented that explore possible physiological mechanisms for the control of cardiac rate by nutritional intake in the pre-weanling rat. The essential properties of the nutrient and the first site of action were studied by using fluids of different pH, osmolality and chemical composition administered intravenously as well as intragastrically. Several probable effector pathways were explored: neuroendocrine (adrenal medullary and adrenocortical, thyroid), cholinergic and adrenergic. Pharmacological blocking agents, surgical removal of glands, replacement hormones and spinal cord trasaction were utilized. Afferent pathways such as vagus and splanchnic systems were approached surgically and the gastrointestinal hormones, histamine, insulin and glucagon, were studied by administration and pharmacological blockade. The evidence tended to rule out a number of possible mechanisms and pathways and to make it appear likely that nutrient acts initially at the gut wall, that the CNS then responds by increasing tone in the classical spinal cardioacceleratory pathways to the beta-adrenergic synapses of myocardium.
The development of susceptibility to immobilization-induced gastric erosions was studied in laboratory rats previously separated from their mothers at 15, 21 or 25 days of age. Early separation (day 15) produced animals whose maximum susceptibility occurred at a much younger age, generated a susceptibility curve over life that was the inverse of the curve for animals separated later and led to severe gastrointestinal hemorrhage as a common and distinguishing complication in younger rats. The pathogenesis of erosion formation in early separated rats may be unique in that, for that group only, the food deprivation component of the immobilization paradigm, when presented alone, also produced erosion of the glandular stomach, with hemorrhage.
Previously published studies point to the behavioral interaction between the mother and her litter as the origin of the processes responsible for the behavioral hyperactivity following maternal separation in 2-week-old rats. The following experiments explore (1) the time course over which behavioral hyperactivity develops, (2) environmental and social determinants, (3) the role of sensory stimulation in the regulation of behavior and (4) the olfactory sensory system as a mediator of separation effects. The hypotheses supported best by the data are (1) that tactile and olfactory stimulation repeatedly provided by the mother act to reduce levels of behavioral arousal of the infants and (2) that maternal separation exerts its effect by withdrawal of this regulating influence, allowing a new level of behavioral arousal, more intrinsic to the infant, to be revealed.
Rat pups, 10-12 days old, survived maternal deprivation if kept warm at 35 degrees, but died within 6 days if allowed to become hypothermic at a room temperature of 23 degrees. Normal body temperatures facilitated feeding, but even without food, warm pups survived starvation longer than cool ones. Increased survival could not be attributed to decreased oxygen consumption, and warm pups lost more body water and solids than cool pups. Striking differences in development that may have affected survival were observed over 72 hr of separation without food. Cool pups showed a virtual arrest of the growth of the tail, fur, tibia, and femur, and failed to increase brain weight, protein, DNA, RNA, and catecholamine contents. Warm pups showed developmental growth more comparable to that of normally mothered pups and significantly exceeded controls in the rate of accumulation of brain norepinephrine and dopamine.
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Although depression and cognitive impairment have been associated with excess mortality following heart surgery, the relationship of these factors to death following treatment for cardiac arrhythmias is unknown. We prospectively examined the associations between biobehavioral factors, mortality, and arrhythmia manageability in 88 patients undergoing programed electrical stimulation for the diagnosis and treatment of supraventricular and ventricular tachyarrhythmias or syncope of unknown origin. Statistically significant relationships were identified between depression and mortality, and between cognitive impairment and mortality. No relationships were observed between cognitive impairment or psychologic profile and arrhythmia severity or treatment efficacy. Our data suggest that arrhythmia morbidity and mortality may in part be a function of cognitive and emotional impairments that lessen the individual's capacity to comply with lifesaving therapy, maintain a stable physiologic milieu, and continue an adaptive emotional life. Failure to recognize the clinical significance of these impairments in patients at risk for sudden cardiac death will contribute to the current difficulty reducing the death and disability associated with cardiac arrhythmias.
OBJECTIVE: To describe how an animal model system can be used to explore basic questions about the nature of loss and the effects of early loss on later vulnerability to disease. METHOD: The physiological and behavioral responses of infant rats to separation from their mothers are first described and then analyzed experimentally into component mechanisms. RESULTS: These studies have revealed an extensive layer of processes underlying the psychological constructs generally used to understand the response to loss. Hidden within the observable interactions of parent and offspring, we found a number of discrete sensorimotor, thermal, and nutrient-based events that have unexpected long-term regulatory effects on specific components of infant physiology and behavior. Release from all of these inhibitory and excitatory regulators together during maternal separation constitutes a novel mechanism by which the experience of loss can be translated into a complex patterned response. Evidence for early regulatory processes has also been found in monkey and human mother-infant interactions. Here they may well constitute the building blocks from which attachment and object representations develop. We and others have found long-term effects of loss, and of selective replacement of regulators, on behavioral development and on later vulnerability to disease. CONCLUSIONS: The results give us a new understanding of early attachment as a developmental force and of human grief as a risk to health.