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M E Stanton

Publications and source records attributed to M E Stanton.

At least 19 recordsLinked to original sources
PubMed1992

Behavioral development following daily episodes of mother-infant separation in the rat.

Use of dermal or inhalation routes of maternal exposure during the postnatal period in rodent developmental neurotoxicity evaluations would be most practical if dams could be separated from their pups during the exposure period. However, this procedure raises questions concerning the effects of mother-infant separation itself on neurotoxicity endpoints. In the present study, Sprague-Dawley rat pups were either maternally deprived in warm incubators for 6 hr each day (7:00 AM-1:00 PM) or left with their dams (control), from Postnatal Day 4-20 (PND4-20), and were tested on a range of endpoints commonly used in developmental neurotoxicology. These included motor activity (PND13, 17, 19, 21, 29, 60), olfactory learning (PND18) and retention (PND25), T-maze delayed alternation (PND23, 24), acoustic startle response (PND23, 62), and auditory thresholds (PND62). None of the behavioral measures were affected by daily separation. Apparently, interrupting the mother-infant interaction for 6 hr/day has little or no effect by itself on behavioral development, as assessed by these measures.

Aging↗
PubMed1992

Eyeblink conditioning in the developing rat.

Long-Evans rat pups, 17-18 or 24 days of age, were trained with an eyeblink conditioning (EBC) procedure that was used previously with adult rats (Skelton, 1988). Pups received 3 sessions of delay conditioning in a single day at about 4-hr intervals (100 trials/session). Trials involved pairings of an auditory conditioned stimulus (2.8-kHz, 82-dB tone) and a periocular-shock unconditioned stimulus (US; 100 ms, 2 mA), which were presented 280 ms apart. EBC was observed at both ages, but older pups learned much more rapidly. Subsequent experiments established that this effect is associative (Experiment 2), that age differences in EBC cannot be attributed to differences in ability to respond or in sensitivity to the US (Experiment 3), and that EBC rate can be modulated by motivational state (Experiment 4). This preparation may help elucidate the relation between neural development and the ontogeny of learning.

Aging↗
PubMed1992

Medial prefrontal cortex lesions and spatial delayed alternation in the developing rat: recovery or sparing?

In Experiment 1, Long-Evans rat pups received medial prefrontal cortex (PFC) aspirations or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform one of two T-maze tasks: discrete-trials delayed alternation (DA) or simple position discrimination. Early PFC damage produced a selective failure to learn the DA task. In Experiment 2, pups given the same lesion or sham surgery were trained on DA on PND19, PND27, or PND33. In relation to sham-operated controls, pups with PFC damage were impaired on PND19, somewhat impaired on PND27, and entirely unimpaired when tested on PND33. In Experiment 3, pups given larger lesions of the frontal cortex on PND10 were impaired on DA when tested on PND23 but not when tested on PND33. These findings indicate that early PFC lesions result in a memory deficit around the time of weaning, which then recovers over the next 10-14 days of development. Moreover, the early deficit is selective for a late developing cognitive process (or processes) that is involved in acquisition of DA.

Aging↗
PubMed1992

Repeated maternal separation in the neonatal rat: cellular mechanisms contributing to brain growth sparing.

Separation of neonates from their dam has been shown to evoke acutely a variety of biochemical responses, typified by depression of ornithine decarboxylase (ODC) activity. In the current study where rat pups were removed from their nursing dams for 6 h, ODC activities in the liver, heart, kidney and lung were markedly suppressed, but the enzyme in the brain was not altered during the early postnatal ages. These data suggest that the brain was protected from maternal separation insults, a homeostatic response mediated in part, by an increase of circulating corticosterone and glycogen mobilization from peripheral tissues, particularly the liver. In addition, we examined whether these responses were extended to pups who were subject to repeated episodes of maternal deprivation, and whether this stress paradigm might be associated with corresponding changes of cellular growth and maturation. Pups were removed from their dams for 6 h daily beginning at 4 days of age until weaning at 21 days. Plasma corticosterone levels of the deprived pups were elevated significantly at the end of each stress episode but returned to basal (control) levels subsequently. The repeating stress paradigm did not influence the magnitude of this hormonal response at the ensuing ages. Consistent with findings observed in the single episodes of stress, ODC activities in the peripheral tissues were significantly depressed in pups subject to repeated maternal deprivation, but the enzyme appeared to recover to control levels 18 h after each insult. In contrast, brain ODC activity did not exhibit any change throughout the period examined. Moreover, while ontogenetic gains of DNA and protein in the peripheral tissues of the deprived rats lagged slightly but consistently behind those of controls, these macromolecules in the brain were not affected appreciably. These results thus suggest that brain growth was, by and large, spared from insults associated with repeated maternal separation; but this stressful paradigm did produce marked, though reversible biochemical and physiological responses in the peripheral tissues of neonates, which cumulatively led to a lag of cellular development.

Animals↗
PubMed1992

Corticosterone hypersecretion in preweanling rats exposed neonatally to trimethyltin.

Developmental neurotoxicity may be influenced by effects of a compound on endocrine function. Here we report that developmental exposure to TMT increases the corticosterone (CS) response to stress in developing rat pups. Long-Evans rat pups were injected i.p. with either 6 mg/kg TMT hydroxide (in 10 microliters/g BW NaCl) or vehicle on Postnatal Day 5 (PND5) or 10 and were then tested for their CS response to restraint stress on PND12, 16, or 20. In the stress test, pups were maternally deprived in individual compartments of an incubator for 24 hr, and then blood sampled by decapitation either immediately (basal), or 30, 60 or 90 min after the onset of a 15-min period of restraint in a wire-mesh holder. Regardless of TMT exposure or age of testing, this procedure produced a peak in plasma CS at 30 min which then recovered to basal levels by 90 min. TMT exposure on PND5 (Experiment 1) resulted in CS hypersecretion relative to vehicle-injected controls on PND12 and 16 but not PND20. TMT exposure on PND10 (Experiment 2) had no effect at PND12 but elevated CS over vehicle controls at PND16 and 20. PND15 exposure to TMT resulted in CS hypersecretion in pups tested on PND20. Neonatal organotin exposure appears to alter CS secretion in a manner that is influenced by age of exposure and age of testing.

Animals↗
PubMed1991

Serial spatial reversal learning in rats: comparison of instrumental and automaintenance procedures.

Serial reversals of a spatial discrimination were trained in rats under automaintenance conditions, in which food reward occurred regardless of responding. This automaintained reversal learning was compared to instrumental reversal learning in other rats trained under a similar procedure which required responding for reward. In the automaintenance (AU) procedure, rats received food after every retraction of a "positive" response lever (S+); retraction of a second, "neutral" lever (So) was not paired with food delivery. Responses to the S+ were elicited at fairly constant rates during daily 100-trial conditioning sessions. Responses to the So occurred early in each session but rapidly diminished across trials. When the valences of the levers were reversed, responding shifted to the new S+ and diminished on the new So. Criterion for reversal was defined as a discrimination ratio (DR) of at least 90% responding to the S+ in two consecutive 10-trial blocks. With repeated reversals, acquisition of criterion performance occurred with increasing rapidity, reaching an asymptote below that required for the original discrimination. A second group of rats was trained on a similar instrumental schedule, in which at least one response to the S+ was required for food delivery. Response rates in this instrumental (IN) group were approximately double those of the AU group. However, ratios of S+ to So response rates were similar to those of the AU group, and the serial reversal curves generated were qualitatively similar. Thus rats can show improvement across serial reversals of a spatial discrimination based entirely on pairings of stimulus events (automaintenance), in a manner similar to that observed in instrumental procedures, in which reward is contingent upon correct responding.

Animals↗
PubMed1991

Fimbria-fornix transections disrupt the ontogeny of delayed alternation but not position discrimination in the rat.

In Experiment 1, Long-Evans rat pups received fimbria-fornix transections or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform either a discrete-trials delayed alternation (DA) or a simple position discrimination (PD) task in a T maze. Rat pups in both surgical conditions learned the PD task within five 12-trial blocks of training. However, only sham-operated pups learned the DA task. In Experiment 2, performance of DA emerged between PND19 and PND27 in sham-operated pups but failed entirely to develop in pups with early lesions. In Experiment 3, fornix-transected pups that were given extended DA training (132 trials) on PND23-PND24 showed some improvement in performance but remained impaired in relation to sham-operated controls. These findings implicate the limbic system in the postnatal development of DA but not PD and suggest that dual-process theories of memory may be relevant to the psychobiology of cognitive development.

Animals↗
PubMed1990

Inhibition of infant glucocorticoid stress response: specific role of maternal cues.

Previous work from this laboratory has shown that passive contact with an anesthetized lactating dam eliminates the corticosteroid stress response to novelty in 12-, 16-, and 20-day-old rat pups. In the present study, we further examined some of the sensory and developmental aspects of this phenomenon. In two experiments, we asked whether inhibition of the corticosteroid stress response is related exclusively to contact with a maternal stimulus as opposed to other social stimuli. Experiment I compared the effectiveness of contact with an anesthetized dam vs, an anesthetized adult male rat. At 12 and 16 days of age, contact with an adult male was somewhat effective in reducing stress responsiveness, whereas at 20 days, contact with an adult male was entirely ineffective. At all ages, contact with an anesthetized dam was an effective inhibitor of the stress response. Experiment II compared the relative effectiveness of contact with an anesthetized dam vs. an anesthetized sibling pup. At all ages, contact with a dam was very effective, whereas contact with an anesthetized pup was entirely ineffective in inhibiting the glucocorticoid stress response. In Experiment III, the effect of maternal contact was assessed during a period of development when the biological, and presumably social, significance of the lactating-dam stimulus is changing. In this study, 20-, 24-, and 28-day-old rat pups revealed a progressive decrement in the ability of maternal contact to inhibit stress responsiveness. These findings replicate and extend our previous ones by showing that maternal stimuli play a special role in the modulation of pituitary-adrenal activity during development.

Animals↗
PubMed1989

Differential ontogeny of working memory and reference memory in the rat.

In two experiments we examined the ability of 15-, 21-, and 27-day-old rats to perform two spatial working memory problems (delayed alternation and discrete-trials delayed alternation) and a reference memory problem (position habit) in a T-maze. In the delayed alternation problem, each animal was presented with a series of free-choice trials and was rewarded for regularly alternating responses to the left and right arms of the T-maze. In the discrete-trials delayed alternation problem, each animal was forced to one maze arm and rewarded (forced run) and was then placed back into the start box and given a choice of arms (choice run). The direction of forced runs followed an irregular, counterbalanced series, and animals were rewarded for choosing the alternate maze arm on choice runs. In the position habit problem, animals were rewarded for consistently choosing one of the two arms of the T-maze. Performance on these problems was assessed relative to control conditions in which reward was not contingent on choice behavior. At all ages, rat pups learned to perform the delayed alternation and position habit problems (Experiment 1). However, only 21- and 27-day-old rats were able to learn the discrete-trials delayed alternation problem. The 15-day-olds were unable to learn this task (Experiment 2). The results of these experiments show that reference memory capacity is present by at least 15 days of age in the rat and does not develop further at later ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Maternal deprivation potentiates pituitary-adrenal stress responses in infant rats.

In three experiments we examined the effect of maternal deprivation on the pituitary-adrenal response of 12-, 16- and 20-day-old rat pups to novelty stress. Infant rats were either deprived individually in heated incubators or left in the home nest with their mother and then tested for their corticosteroid response to 30-min exposure to a novel test arena (novelty-stress). In Experiment 1 we showed that the magnitude of the stress response was a positively accelerated function of the deprivation interval. Stress responses were not increased after 1 hour of deprivation, were modestly increased after 8 hours of deprivation, and were dramatically increased after 24 hours of deprivation. In Experiment 2 we asked whether potentiation of the stress response resulted from the maternal or the nutritive components of the deprivation procedure. Pups were tested under one of four treatment conditions formed by a 2 (Maternally Deprived vs. Nondeprived) x 2 (Nutritively Deprived vs. Nondeprived) factorial design. At 12 and 16 days of age, potentiation of the stress response was traced to the absence of maternal care and not nutrients. At 20 days of age, both maternal and nutritive deprivation contributed to the potentiated stress response. The results of Experiment 3 showed that this effect was mediated, at least in part, by increased adrenocortical sensitivity to ACTH, because the corticosteroid response to exogenous ACTH administration was also increased by maternal deprivation. These findings add to a growing body of literature that supports the concept of maternal regulation of infant physiology. They also support previous reports from this laboratory indicating that suppression of the pituitary-adrenal system is modulated by maternal variables during the preweaning period in the rat.

Age Factors↗
PubMed1987

Maternal contact inhibits pituitary-adrenal stress responses in preweanling rats.

Three experiments examined psychological factors which inhibit pituitary-adrenal activity in 12-, 16-, and 20-day-old rats. Infant rats were placed in heated novel test arenas for 30 min--a treatment which increases corticosterone secretion--and were presented with different appetitive stimuli in order to determine whether these stimuli inhibit this increased hormone secretion. The first experiment was a factorial combination of two conditions: suckling an anesthetized dam and milk ingestion through an intraoral cannula. At all ages, suckling inhibited corticosterone secretion but milk ingestion did not, nor was there an interaction of these factors. In the second experiment, the importance of suckling was assessed by allowing pups' contact with an anesthetized dam either with or without the opportunity to suckle. At all ages, contact with suckling and contact alone were equally effective in inhibiting corticosterone secretion. The third experiment asked whether contact with a lactating female is necessary for pituitary-adrenal inhibition or whether more distal cues associated with lactation are sufficient. Pups were tested under one of four treatments formed by a 2(Lactating vs. Virgin Female) X 2(Contact vs. No Contact) factorial design. At all ages inhibition of corticosterone secretion occurred only in animals which were allowed contact with an anesthetized female. Lactating and virgin females were equally effective for the 12- and 16-day-old pups, but contact with a virgin female was less effective for the 20-day-old pups. These findings indicate that neuroendocrine mechanisms subserving inhibition of the pituitary-adrenal system exist during the preweanling period in the rat, and suggest the possibility of maternal regulation of this physiological system during development.

Animals↗
PubMed1987

Behavioral stress impairs long-term potentiation in rodent hippocampus.

A number of hormones secreted from the pituitary-adrenal system during stress affect learning and memory processes. The phenomenon of hippocampal long-term potentiation (LTP) is viewed by many as a putative mechanism of memory storage and has proved a most valuable model for study of neuronal plasticity at the cellular level. The present study was conducted to investigate the possibility that stressful events which occur prior (in vivo) to the preparation of brain slices may influence the electrophysiology of the in vitro hippocampal explant when tested for LTP. Adult male rats (Long-Evans male X Sprague-Dawley female) were pair-housed 1 week prior to testing. One animal in each pair was either placed in a restraining tube for 30 min and received no tail shocks (Restraint) or placed in a restraining tube and received tail shocks (1 microA, 1 s) every minute for 30 min (Restraint + Shock). The other animal in each pair was taken directly from the home cage and received no restraint or tail shock (Control). In vitro hippocampal slices were then prepared immediately from these animals according to standard methods. Our results demonstrate a marked impairment of LTP in hippocampal explants taken from rats exposed to stress. The significance of this result with respect to cellular mechanisms underlying the relationship between stress, cognition, and learning is discussed.

Animals↗
PubMed1985

Pharyngeal polyps in two feline siblings.

Pharyngeal polyps were diagnosed in 2 sibling kittens referred for evaluation of chronic upper respiratory tract disease. Surgical excision of the masses was performed in both kittens after skull radiography and oral examination. One kitten had a recurrence of pharyngeal polyps 5 weeks after surgery and was euthanatized and necropsied. The clinical and histologic findings in these 2 cases suggested a congenital origin of this disease.

Animals↗
PubMed1985

Brief separation elevates cortisol in mother and infant squirrel monkeys.

The pituitary-adrenal response of mother and infant squirrel monkeys was assessed under basal conditions and after 5, 10, or 20 min of separation followed by 30 min of reunion. All separation conditions produced equal increments of cortisol (approximately 50%) in both mothers and infants. These increments were lower than would have occurred in the absence of reunion. These results extend previous reports that reunion ameliorates the psychoendocrine effects of separation and indicate that mother-infant attachment can be studied with shorter periods of separation than have been used customarily.

Animals↗
PubMed1985

Social influences on conditioned cortisol secretion in the squirrel monkey.

'Social buffering'--the apparent capacity of group membership to reduce the adrenocortical response to stress, was investigated in squirrel monkeys by means of a between-within experimental design. Adult males were assigned to two groups. Group paired (n = 6) received pairings of a conditional stimulus (CS) with footshock. Group control (n = 6) received CS presentations without shock. All animals were then tested with 10 presentations of the CS without shock under three social-housing conditions, in four successive phases of the experiment: individual, dyad, group, and individual housing. Neither group showed a cortisol response to the CS prior to training. Following training, CS-evoked elevations of cortisol were found only in group paired, and only in the individual housing conditions. These results replicate and extend our previous finding that the presence of conspecifics can ameliorate a neuroendocrine response to psychological stressors in squirrel monkeys.

Animals↗
PubMed1977

Harvey Cushing: "From tallow dip to television".

Harvey Cushing was not only a leading founder of neurosurgery, but his work in general surgery provoked research which advanced medical knowledge, and he made substantial contributions to medical education and general literature. He discovered (with L.E. Livinggood) that the stomach and small intestine could be rendered sterile by fasting before operations; he successfully sutured the cervical thoracic duct without subsequent leakage; he suggested, after attempted repair of chronic valvular lesions in the dog, the possibility of surgery on cardiac valves in man; he demonstrated the relation of intracranial pressure to blood pressure; he devised one of the first charts for recording pulse and respiration and introduced routine blood pressure determinations during operation; and he stimulated continuing research by internists and endocrinologists through his work on the pituitary body and its disorders-work which was crowned by his discovery of pituitary basophilism. His unique course in operative surgery for medical students at the Johns Hopkins was adopted by other medical schools and he advanced other provocative theories concerning the organization and content of the medical curriculum. He provided elective clinics at Harvard Medical School for students and established postgraduate fellowships at the Hopkins, Harvard, and Yale schools of medicine. Cushing brought distinction upon himself and the medical profession through his books and essays of high literary quality and originality, most notably his biography of Sir William Osler, which was awarded a Pulitzer Prize in 1926.

Education, Medical, Graduate↗