The calming effect of stimuli presentation on infant Japanese Macaques (Macaca fuscata) under stress situation: a preliminary study

In human newborns, presentation of sounds and odors under stress situations had a calming effect on behavioral and cortisol responses (Kawakami et al., 1996, 1997). These calming effects were examined with 10-day- and 15-day-old Japanese macaques. In Study 1, white noise presentation (Experimental conditions) at the blood sampling was compared with no sound presentation (Control conditions) at the blood sampling. White noise presentation has a calming effect on coded behavioral responses. In Study 2, lavender scent presentation (Experimental conditions) at the blood sampling was compared with no odor presentation (Control conditions) at the blood sampling. Lavender presentation has a calming effect on cortisol responses in the marginal level. From the data of these studies, the salivary cortisol levels were related to the cortisol levels in plasma. Our results may suggest the different effects of sound and odor on infant Japanese macaques.     

Recurrent long-lasting tethering reduces BDNF protein levels in the dorsal hippocampus and frontal cortex in pigs

Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the onset of depression and in antidepressant efficacy, although the exact role of this neurotrophin in the pathophysiology of depression remains to be elucidated. Also, the interaction between chronic stress, which may precede depression, corticosteroids and BDNF is not fully understood. The present study aimed at investigating whether long-lasting, recurrent tethering of sows during a period of 1.5 or 4.5 years leads to enduring effects on measures that may be indicative of chronic stress, compared with animals kept in a group housing system ('loose' sows). Immediately after slaughter, the frontal cortex, dorsal and ventral hippocampus were dissected and protein levels of BDNF and its receptors were analyzed and compared with plasma cortisol levels and adrenal weights. Results indicate that tethering stress reduced BDNF protein levels in the dorsal hippocampus and the frontal cortex, but not in the ventral hippocampus. In addition, levels of TrkB, the high affinity receptor for BDNF, were increased in the dorsal hippocampus. Plasma cortisol levels and adrenal weight were increased after tethering. These stress effects on BDNF levels were more pronounced after 4.5 years of recurrent tethering and negatively correlated in particular in the frontal cortex with cortisol levels and adrenal weight. This suggests that the stress effect of tethered housing on neurotrophin levels may be mediated via cortisol. Taken together, these data indicate that recurrent tethering stress in sows over 4.5 years results in a loss of neurotrophic support by BDNF, mediated by an overactive neuroendocrine system.     

Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants

A functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene has been associated with variation in anxiety and hypothalamus-pituitary-adrenal (HPA) axis function in humans and rhesus macaques. Individuals carrying the short allele are at a higher risk for developmental psychopathology, and this risk is magnified in short allele carriers who have experienced early life stress. This study investigated the relationship between 5-HTTLPR allelic variation, infant abuse, and behavioral and hormonal responses to stress in rhesus macaques. Subjects were 10 abusive mothers and their infants, and 10 nonabusive mother-infant pairs. Mothers and infants were genotyped for the rh5-HTTLPR, and studied in the first 6 months of infant life. For mothers and infants, we measured social group behavior, behavioral responses to handling procedures, and plasma concentrations of ACTH and cortisol under basal conditions and in response to stress tests. The proportion of individuals carrying the short rh5-HTTLPR allele was significantly higher among abusive mothers than controls. Among mothers and infants, the short allele was associated with higher basal cortisol levels and greater hormonal stress responses in the infants. In addition, infants who carried the short rh5-HTTLPR allele had higher anxiety scores than infants homozygous for the long allele. The rh5-HTTLPR genotype also interacted with early adverse experience to impact HPA axis function in the infants. These results are consistent with those of previous studies which demonstrate associations between serotonergic activity and anxiety and stress reactivity, and add additional evidence suggesting that genetic variation in serotonergic function may contribute to the occurrence of abusive parenting in rhesus macaques and modulate emotional behavior and HPA axis function.     

ACTH and glucocorticoid responses under two conditions of stress in macaques

Female macaques were tested under two different psychologically stressful situations in which plasma ACTH and glucocorticoid concentrations were measured. In the first, animals were operantly trained to enter a small transport cage over a four-week period, and plasma ACTH and glucocorticoids were measured in response to brief confinement in the cage before and after training. ACTH values were significantly lower in the pre-test (stress) condition when compared to those for the post-test, whereas the opposite result was found for glucocorticoid values. In the second experiment, blood samples were collected before and one hour after exposure to more acute and severe stress (restraint, venipuncture, handcapture, transport). Both ACTH and glucocorticoid values were significantly elevated from baseline at the post-test sample. The differential relationship between the two hormones among the two experiments was likely the result of the specific timing and magnitude of the stress imposed by each test situation.     

Plasma cortisol stress response in fingerling rainbow trout, Salmo gairdneri Richardson, to various transport conditions, anaesthesia, and cold shock

Plasma cortisol levels of fingerling rainbow trout were measured as an index of the stress resulting from various procedures used for transport of the fish for stocking. When transported under 'normal' conditions, which included water at the hatchery acclimation temperature (10–11°C), O₂ saturation or supersaturation, and neutral pH, there was a marked increase in plasma cortisol levels within 0.5 h, which was maintained over the next 4 h of transport; there was a significant decrease in plasma cortisol by 8 h of transport. It was found that the plasma cortisol levels at 4 and 8 h were not appreciably altered by transport under partial O₂ desaturation, O₂ saturation, O₂ supersaturation, or 0.5% NaCl, or by anaesthesia with tricaine methanesulfonate (MS 222) prior to capture and transport in MS 222-free water or 0.5% NaCl. A 15 min exposure to an immobilizing dose of buffered or unbuffered MS 222, or 2-phenoxyethanol, caused an increase in plasma cortisol of about 2 h duration, indicating that anaesthetics are themselves stressful. Exposure to chilled water (1° C) caused a large increase in plasma cortisol levels by 4 h after initiation of exposure; plasma cortisol had decreased at 1 day, and by 2 days a constant level was reached which was above the level in fingerling trout under 'normal' hatchery conditions. Trout acclimated to chilled water for 24 h and transported in chilled water had an increase in plasma cortisol during transport. Anaesthesia prior to transport or addition of salt did not reduce the stress of transport as judged by plasma cortisol levels. The results indicate that stress from capture and transport during stocking cannot be avoided using present methods.     

Effects of reproductive condition and dominance rank on cortisol responsiveness to stress in free‐ranging female rhesus macaques

The hypothalamic–pituitary–adrenal (HPA) axis modulates individuals' physiological responses to social stress, which is an inevitable aspect of the daily lives of group‐living animals. Previous nonhuman primate studies have reported that sex, age, rank, and reproductive condition influence cortisol levels under stressful conditions. In this study we investigated cortisol responses to stress among 70 multiparous, free‐ranging female rhesus macaques (Macaca mulatta) on the island of Cayo Santiago, PR. Plasma cortisol samples were collected in two consecutive years under similar conditions. Twenty‐two females were sampled both years, and most of those females were lactating in only one of the years. Individual differences in cortisol levels were stable across years, even though reproductive condition changed for most individuals. No relationship was found between age or social rank and cortisol levels. Of the females that changed reproductive conditions, cortisol levels were higher when they were lactating than when they were cycling, and the amount of change in cortisol from cycling to lactating was greatest for low‐ranking individuals. Heightened reactivity to stress during lactation may be the result of concerns about infant safety, and such concerns may be higher among low‐ranking mothers than among higher ranking mothers. Psychosocial stress and hyperactivation of the HPA axis during lactation can suppress immune function and increase vulnerability to infectious diseases, thus explaining why adult females in the free‐ranging rhesus macaque population on Cayo Santiago have a higher probability of mortality during the birth season than during the mating season. Am. J. Primatol. 72:559–565, 2010. © 2009 Wiley‐Liss, Inc.     

Urinary cortisol responses of longtailed macaques to five cage sizes,tethering, sedation,and room change

Urinary free cortisol responses to five cage sizes, cage level, room change, tethering adaptation, chronic catheterization, and ketamine sedation were measured in 14 female and 14 male wild-born adult Macaca fascicularis. Urinary free cortisol, a physiological measure of psychological well-being that can be collected unobtrusively, provided a measure of the animals' general adrenocortical response to various conditions over a time course of hours. Urinary free cortisol values in response to stimulation with adrenocorticotropic hormone (ACTH) validated the measure as a reflection of blood values. Cortisol values were expressed as a ratio to creatinine, which normalized for differences in urinary output and body weight (muscle mass). Cage size (20–140% of regulation floor area) and housing level (upper vs. lower cage) had no effect on stress, as measured by cortisol excretion. Room change elicited a slight increase in cortisol excretion for the first day, but not to a level suggesting stress. Sedation, surgery, some aspects of tethering adaptation, and chronic catheterization produced urinary cortisol evidence of stress. Even so, animals varied in their responses and all showed adaptation. Males and females did not differ in normal mean values but females tended to have higher cortisol levels in response to potential stressors investigated in this study. Cortisol levels continued to decline gradually throughout the study. © 1993 Wiley-Liss, Inc.     

Behavior, appetite, and urinary cortisol responses by adult female pigtailed macaques to cage size, cage level, room change, and ketamine sedation

Pigtailed macaques (Macaca nemestrina) and longtailed macaques (M. fascicularis) show behavioral, ecological, and possible temperament differences, and their responses to the laboratory environment might therefore be quite different. We tested pigtailed macaques under the same conditions that were investigated in a previous study with longtailed macaques, using the same comprehensive set of physiological and behavioral measures of stress. First, eight adult females' adaptation to a new room in regulation-size cages was monitored, and in the third week their responses to ketamine sedation were measured. Then they spent two weeks singly housed in each of four cage sizes (USDA regulation size, one size larger, one size smaller, and a very small cage). Half of the subjects were in upper-level cages and the remainder in lower-level cages for the entire study. Cage size, ranging from 20% to 148% of USDA regulation floor area, was not significantly related to abnormal behavior, self-grooming, manipulating the environment, eating/drinking, activity cycle, cortisol excretion, or biscuit consumption. Locomotion and frequency of behavior change were significantly reduced in the smallest cage, but did not differ in cage sizes ranging from 77% to 148% of regulation size. The only manipulation to produce an unequivocal stress response, as measured by cortisol elevation and appetite suppression, was ketamine sedation. Room change and cage changes were associated with minimal cortisol elevation and appetite suppression. Wild-born females showed more appetite suppression after room change than captive-born females. No differences were related to cage level. Pigtailed macaques strongly resembled longtailed macaques except they showed weaker responses to the new room and cage change, probably because the pigtails had spent more time in captivity. These findings support the conclusion that increasing cage size to the next regulation size category would not have measurable positive effects on the psychological well-being of two species of laboratory macaques.     

Cortisol can increase the susceptibility of brown trout, Salmo trutta L., to disease without reducing the white blood cell count

Chronic elevation of plasma cortisol levels in the brown trout by means of slow-release, intraperitoneal implants increased the susceptibility of the fish to disease. Elevation from a mean basal level of 1–4ng ml⁻¹ to ∼10ngml⁻¹ for a period of 2–4 weeks was sufficient to increase the mortality rate due to furunculosis, Saprolegnia infection and bacterial fin-rot. This level of plasma cortisol is well within that capable of being produced by the fish under conditions of chronic stress. The increase in susceptibility to disease was not accompanied by a reduction in the number of circulating lymphocytes and it is suggested that under certain conditions chronically-elevated cortisol levels may be more sensitive, predictive indicators of reduced disease-resistance than are changes in blood cell counts.     

Development of the hormonal reaction to stress in the ontogenesis of the baboon Papio hamadryas

The hormonal reaction of adrenal and gonadal glands of baboons at various ages was studied under 2 hr immobilization stress condition. Concentrations of cortisol, 11-deoxycortisol, 17-hydroxypregnenolone, dehydroepiandrosterone and testosterone were determined by radioimmunoassay in the monkey blood plasma at different times during the stress reaction. A more pronounced reaction of adrenal cortex was shown in 1 year old baboons. The peak of cortisol level in immature monkeys under stress conditions was registered much earlier than in adult monkeys.     

Individual differences in peripheral blood immunological and hormonal measures in adult male rhesus macaques (Macaca mulatta): Evidence for temporal and situational consistency

A growing body of research has indicated that consistent individual differences exist in physiological systems with which the immune system interacts. Few data have been reported that demonstrate stable individual differences in immunological measures, however. In the present study, enumerative measures of immune system activity were examined in 36 adult male rhesus macaques over a 13 month period under baseline conditions as well as under conditions of pharmacological and physical challenge. Blood samples were assayed for plasma concentrations of ACTH and cortisol, as well as neutrophil, total lymphocyte, CD4+ and CD8+ lymphocyte numbers, and the CD4/CD8 ratio. Analyses revealed that individual differences in the CD4/CD8 ratio and, to a lesser extent, plasma ACTH and cortisol concentrations, and neutrophil and CD4+ lymphocyte numbers were consistent across situations and times, despite changes in mean values during the various blood sampling sessions. The results suggest that the CD4/CD8 ratio might be considered trait-like and a useful immunological measure of biobehavioral organization. Am. J. Primatol. 44:29–41, 1998. © 1998 Wiley-Liss, Inc.     

Working with rather than against macaques during blood collection

Training macaques to cooperate during blood collection is a practicable and safe alternative to the traditional procedure implying forced restraint. It takes a cumulative total of about 1 hr to train an adult female or adult male rhesus macaque successfully to present a leg voluntarily and accept venipuncture in the homecage. Cooperative animals do not show the significant cortisol response and defensive reactions that typically occur in animals who are forcibly restrained during this common procedure.     

季节和等级顺位对雄性黄山短尾猴粪样皮质醇水平的影响

在长期的进化选择压力下,灵长类动物大多数群居生活,群体中的动物个体也面临来自群内成员强度不一的社会压力,压力大小的重要生理指标通常用其体内的皮质醇水平的变化来衡量.季节性繁殖的黄山短尾猴(Macaca thibetana),群体内的个体有严格的社会等级,是研究等级顺位与社会压力水平之间关系的理想研究对象.我们采集13只...     

Coat condition, housing condition and measurement of faecal cortisol metabolites--a non-invasive study about alopecia in captive rhesus macaques (Macaca mulatta)

BACKGROUND: Previous studies have characterized alopecia in captive rhesus macaques (Macaca mulatta) by a mixed partial to complete alopecia in a bilateral symmetric pattern. METHODS: In this study, coat condition assessments were related to exogenous and endogenous factors in captive rhesus macaques under different housing conditions in order to identify disturbances in environmental factors controlling or influencing hair growth. Additionally, the degree of alopecia was investigated in relation to adrenal endocrine function as an indicator of social stress using faecal glucocorticoid measurements. RESULTS: Hair loss was found to vary with season and sex, was most pronounced in adult females during the winter and spring months. Generally, infants were not affected, but alopecia developed during adolescence. However, the housing system, available enclosure space and variations in group size and composition also appeared to influence coat condition. Levels of immunoreactive cortisol metabolites (11-oxoetiocholanolone) in faeces were significantly negatively correlated with alopecia, suggesting a relationship between hypothalamic-pituitary-adrenal (HPA) axis activity and hair loss in captive rhesus macaques. CONCLUSIONS: Although the present study demonstrates the influence of the HPA axis on coat condition, it is not known if hair loss is caused by abnormal behaviour or hormonal imbalances of the HPA axis itself. Our data suggest that alopecia in rhesus macaques is a highly complex multicausal disorder.     

Plasma cortisol responses to stress in lactating and nonlactating female rhesus macaques

Lactating female rats without their pups exhibit lower HPA responsiveness to stress than nonlactating females. However, responsiveness to stress is similar when lactating females are tested with their pups and the stressor involves a potential threat to the offspring. This study constitutes the first comparison of stress responsiveness in lactating and nonlactating female nonhuman primates. Subjects were 53 multiparous female free-ranging rhesus macaques. Approximately half of the females were lactating and half were nonpregnant/nonlactating. Blood samples were obtained after capture and after overnight housing in an individual cage. Lactating females were tested with their infants. Lactating females had significantly higher plasma cortisol levels than nonlactating females on both days. Having or not having an infant was also a better predictor of plasma cortisol levels among all females than their age, dominance rank, group of origin, time of day at which the sample was obtained, and time elapsed since beginning of the sampling procedure or since anesthesia. Plasma cortisol levels of lactating females were not significantly correlated with post-partum stage or with the cortisol levels of their infants. Capture, handling, and individual housing in a cage are powerful psychological stressors for free-ranging primates. We suggest that the higher plasma cortisol levels exhibited by lactating females reflect greater responsiveness to stress associated with perception of risks to infants. Hyporesponsiveness to stress may not be a general characteristic of lactation in all mammalian species, but a short-term effect of infant suckling that is most apparent with stressors unrelated to the offspring.     

Plasma cortisol and corticosterone concentrations in the golden hamster, (Mesocricetus auratus)

Because some recent studies of hamster adrenocortical function have depended on older studies that may have been inadequate or misinterpreted, the present study re-examined plasma corticosterone and cortisol concentrations in hamsters under several conditions to determine which plasma glucocorticoid predominated in this animal. Sensitive radioimmunoassays were used to measure separately the two glucocorticoids in the basal condition, after adrenocorticotropin (ACTH) treatment, after acute stress, and after chronic stress. In the basal condition, corticosterone concentrations were 3-4 times higher than those of cortisol. After stimulation, this difference disappeared, but rarely were any hamster's cortisol levels higher than their corticosterone levels. Both ACTH and acute stress elevated plasma corticosterone and cortisol concentrations, but only plasma cortisol concentrations were elevated following chronic stress. The dissociation between cortisol and corticosterone concentrations after chronic stress suggests that the two glucocorticoid hormones in the hamster may be regulated independently. The data also indicate that both corticosterone and cortisol should be measured when assessing adrenocortical function in the hamster.     

Circadian rhythm in circulating CD16-positive natural killer (NK) cells in macaque monkeys,implication of plasma cortisol levels

The daily change in both percentage and absolute number of circulating major lymphocyte subset was determined with young Japanese monkeys and rhesus monkeys. The blood sample was collected at four hour-intervals beginning at 16:00 for 24 hours under the condition of applying tethering system by which blood samples could be collected without restraint. During the dark period (from 20:00 to 08:00), the number of peripheral lymphocytes increased and that of granulocytes decreased, resulting in no significant change in the number of total peripheral white blood cells. The absolute number of CD4 + T, CD8 + T, and CD20 + B cells showed the significant daily change similar to that in number of peripheral lymphocytes, indicating no proportional change in these subsets. The typical proportional change was observed in CD16 + natural killer (NK) cells and the percentage of CD16 + cells decreased during dark period (from 20:00 to 04:00) and increased in the morning (from 08:00 to 12:00). The NK activity determined by killing K562 target cells showed the same changing pattern as that of percentage in CD16+ NK cells. The changing pattern of both percentage and activity of NK cells was consistent with that of plasma cortisol levels. In addition, the intravenous injection of 300 μg/kg of cortisol induced increase in plasma cortisol levels and decrease in percentage of CD16 + NK cells during the first 60 min after cortisol injection. These results strongly suggest that the levels of peripheral functional CD16 + NK cells might be directly regulated by plasma cortisol level in macaque monkeys.     

Leptin, gastrointestinal and stress hormones in response to exercise in fasted or fed subjects and before or after blood donation.

Leptin, an ob gene product of adipocytes, plays a key role in the control of food intake and energy expenditure but little is known about leptin response to strenuous exercise in fasted and fed subjects or before and after blood donation. This study was designed to determine the immediate effects of strenuous exercise in healthy volunteers under fasting or fed conditions and before and one day after blood donation (450 ml) on plasma levels of leptin and gut hormones [gastrin, cholecystokinin (CCK), pancreatic polypeptide (PP) and insulin], as well as on "stress" hormones (cortisol, catecholamines and growth hormone. Two groups (A and B) of healthy non-smoking male volunteers were studied. All subjects performed incremental exercise tests until exhaustion (up to maximal oxygen uptake--VO2max), followed by 2 h of rest session. Group A perfomed the tests on a treadmill, while group B on a cycloergometer. In group A, one exercise was performed under fasting conditions and the second following ingestion of a standard liquid meal. In group B, one exercise test was performed as a control test and the second 24 h after blood donation (450 ml). Blood samples were withdrawn 5 min before the start of the test, at the VO2max, and 2 h after finishing the exercise. No significant change in plasma teptin were observed both immediately and 2 h after the exercise in fasted subjects, but after the meal the plasma leptin at VO2max and 2 h after the test was significantly higher, while after blood donation was significantly reduced. The postprandial rise in plasma leptin was accompanied by a marked increment in gut hormones; gastrin, CCK and PP and stress hormones such as norepinephrine, cortisol and GH. These hormonal changes could contribute to the postprandial rise in plasma leptin concentrations, while the fall of leptin after blood donation could be attributed to the inadequate response of stress hormones and autonomic nervous system to exhausting exercise. We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation and 3) following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, cortisol and GH concentrations, possibly due to the impairment in the autonomic nervous control of these hormones.     

The repeated procedure of weaning and peer group formation causes accumulation of stress and changes of plasma cortisol level and natural killer activity in squirrel monkeys (Saimiri sciureus)

The psychological stress was evaluated in repeated and unrepeated procedures of weaning as well as forming peer group in squirrel monkeys. The repeated procedure included the process of increasing the period of separation or formation stepwise during four weeks. The plasma cortisol levels and natural killer (NK) activities were monitored during experiment to evaluate the stress in infant monkeys. The plasma cortisol level rapidly increased two to three times as much as basal level and kept high levels throughout experiment in repeated group. In the infants of unrepeated group, significant increase of cortisol level and decrease of NK activity were observed in day-1, but both of them returned to the basal level at day-7. Both cortisol level and NK activity did not show any change with exception of decrease in NK activity at day-7 in infants who were introduced into peer group without repeated procedure. On the other hand, both cortisol level and NK activity increased during the repeated procedure. These results indicate that both weaning and forming peer group induce the psychological stress in infant squirrel monkeys, resulting in changes of plasma cortisol level and NK activity. Repeating the procedure of separation or introduction applied in this study caused the accumulation of stress. Although plasma cortisol level increased in infants exposed to both weaning and forming peer group, the changing pattern of NK activity differed between them. This finding suggests that social or psychological stress show two different effects on immune function, suppression, and enhancement depending on the level of stress.