Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction (original) (raw)
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Biological Psychiatry, 1996
concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropinreleasing hormone ( oCRH), and A CTH l_24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and~or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.
Stress, the HPA axis, and nonhuman primate well-being: A review
Applied Animal Behaviour Science, 2013
Numerous stressors are routinely encountered by wild-living primates (e.g., food scarcity, predation, aggressive interactions, and parasitism). Although many of these stressors are eliminated in laboratory environments, other stressors may be present in that access to space and social partners is often restricted. Stress affects many physiological systems including the hypothalamic-pituitary-adrenocortical (HPA) axis, which is the focus of this review. The glucocorticoid, cortisol, is the ultimate output of this system in nonhuman primates, and levels of this hormone are used as an index of stress. Researchers can measure cortisol from several sampling matrices that include blood, saliva, urine, faeces, and hair. A comparison of the advantages and disadvantages of each sampling matrix is provided to aid researchers in selecting an optimal strategy for their research. Stress and its relationship to welfare have been examined in nonhuman primates using two complimentary approaches: comparing baseline cortisol levels under different conditions, or determining the reactivity of the system through exposure to a stressor. Much of this work is focused on colony management practices and developmental models of abnormal behaviour. Certain colony practices are known to increase stress at least temporarily. Both blood sampling and relocation are examples of this effect, and efforts have been made to reduce some of the more stressful aspects of these procedures. In contrast, other colony management practices such as social housing and environmental enrichment are hypothesized to reduce stress. Testing this hypothesis by comparing baseline cortisol levels has not proved useful, probably due to "floor" effects; however, social buffering studies have shown the powerful role of social housing in mitigating reactions of nonhuman primates to stressful events. Models of abnormal behaviour come from two sources: experimentally induced alterations in early experience (e.g., nursery rearing), and the spontaneous development of behavioural pathology (e.g., self-injurious behaviour). Investigators have often assumed that abnormal behaviour is a marker for stress and thus such monkeys are predicted to have higher cortisol levels than controls. However, an emerging finding is that monkeys with abnormal behaviour are more likely to show a pattern of lowered cortisol concentrations which may reflect either an altered set point or a blunting of the stress response system. These findings parallel human clinical studies demonstrating that neuropsychiatric disorders may be associated with either increased or decreased activity of the HPA system, depending on the aetiology and manifestation of the disorder and their potential influence in provoking allostatic shifts in system functioning.
Proceedings of the National Academy of Sciences of the United States of America, 2006
The stress inoculation hypothesis presupposes that brief intermittent stress exposure early in life induces the development of subsequent stress resistance in human and nonhuman primates. Rodent studies, however, suggest a role for maternal care rather than stress exposure per se (i.e., the maternal mediation hypothesis). To investigate these two hypotheses, we examined maternal care and the development of stress resistance after exposure to brief intermittent infant stress (IS), mother-infant stress (MIS), or no stress (NS) protocols administered to 30 monkeys between postnatal weeks 17 and 27. Unlike rodents, the IS condition did not permanently increase primate maternal care, nor did measures of total maternal care predict subsequent offspring hypothalamicpituitary-adrenal-axis responsivity. Although MIS infants received less maternal care than IS and NS infants, both IS and MIS monkeys developed subsequent stress resistance. These findings indicate that rearing differences in the development of stress resistance are more closely related to differences in prior stress exposure than to differences in maternal care. A second experiment confirmed this conclusion in a different cohort of 25 monkeys exposed as infants to high foraging-demand (HFD) or low foraging-demand (LFD) conditions. HFD infants exhibited intermittent elevations in cortisol levels and received less maternal care than LFD infants. In keeping with a key prediction of the stress inoculation hypothesis, HFD males responded to stress in adulthood with diminished hypothalamic-pituitary-adrenal-axis activation compared with LFD males. Results from both experiments demonstrate that stress inoculation, rather than high levels of maternal care, promotes the development of primate stress resistance. hypothalamic-pituitary-adrenal axis ͉ monkey ͉ maternal care ͉ resilience Conflict of interest statement: No conflicts declared.
Psychosocial Stress and Urinary Cortisol Excretion in Marmoset Monkeys
Physiology & Behavior, 1997
SMITH, T. E. AND J. A. FRENCH. Psychosocial stress and urinary cortisol excretion in marmosets (Callithrix kuhli). PHYSIOL BEHAV 62(2) 225-232, 1997.-Activation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the hallmarks of the physiological responses to psychosocial stressors. The most common method of assessing HPA function is via the measurement of plasma cortisol levels. However, venipuncture involves capture and restraint, which can modify HPA function. We validated a noninvasive procedure for monitoring HPA responses to stressors by measuring excretion of free urinary cortisol. Samples collected throughout the day displayed marked circadian variation, with low cortisol values in first-void samples, followed by a midmorning peak in cortisol excretion. Concentrations of excreted cortisol declined throughout the day. Exposing marmosets to mild and moderate stressors (11 h isolation in a small cage and manual restraint) increased excreted cortisol concentrations in a dosedependent fashion: isolation in a small cage led to elevated cortisol in afternoon samples, while manual restraint and isolation produced elevated cortisol in both morning and afternoon samples. The marmoset HPA is differentially sensitive to rather subtle variations in stressors, and these results show that urinary cortisol excretion is a valid and sensitive index of the HPA response to these stressors.
Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys
Proceedings of the National Academy of Sciences, 2011
Maternal separation (MS), which can lead to hypothalamic pituitary adrenal axis dysfunction and behavioral abnormalities in rhesus monkeys, is frequently used to model early adversity. Whether this deleterious effect on monkeys is reversible by later experience is unknown. In this study, we assessed the basal hair cortisol in rhesus monkeys after 1.5 and 3 y of normal social life following an early separation. These results showed that peerreared monkeys had significantly lower basal hair cortisol levels than the mother-reared monkeys at both years examined. The plasma cortisol was assessed in the monkeys after 1.5 y of normal social life, and the results indicated that the peak in the peerreared cortisol response to acute stressors was substantially delayed. In addition, after 3 y of normal social life, abnormal behavioral patterns were identified in the peer-reared monkeys. They showed decreases in locomotion and initiated sitting together, as well as increases in stereotypical behaviors compared with the mother-reared monkeys. These results demonstrate that the deleterious effects of MS on rhesus monkeys cannot be compensated by a later normal social life, suggesting that the effects of MS are long-lasting and that the maternal-separated rhesus monkeys are a good animal model to study early adversity and to investigate the development of psychiatric disorders induced by exposure to early adversity. time profile | unbound fraction of cortisol | activity | repetitive action | social affiliative behavior I n humans, early adversity can have long-term effects on the brain and behavior of animals, which increases vulnerability to the development of psychopathology. For example, studies have demonstrated abnormal behavior in adults who were mistreated as children (1, 2). In monkeys, maternal separation (MS) is frequently used to mimic early adversity. In a study using 6-d MS Tonkean macaques, self-injurious behavior was observed and social play decreased during the 9 wk following separation (3). Early separation often resulted in abnormally aggressive and reproductive activity (4). Another study that examined the marmoset demonstrated decreased motor activity and body contact in MS monkeys compared with controls .
Rearing experience, stress and adrenocorticosteroids in the rhesus monkey
Physiology & Behavior, 1972
BEHAV. 8 (2) 339-343, 1972.-Baseline cortisol levels and adrenocortical response to ACTH admimstration and chairrestraint stress were measured in rhesus monkeys reared under partial social isolation, total social isolation, and jungle conditions, 3-4 years after the rearing treatments. In contrast to expectations derived from the rodent literature on early treatment effects, no pituitary-adrenocortlcal effects of rearing condition were found in the monkey. From these and other data, it seems that such effects which may appear shortly after rearing treatment in the monkey are transient, and there is no long-term modification of a hormonostat mechanism regulating basal cortisol levels or adrenocortical responsivity. Other effects of stress were observed; additionally, some sex differences were noted. Adrenocortical secretion apparently fell to zero soon after termination of stress and did not recommence within the next 2 hr, indicating a rapid and complete poststress reset of some feedback mechanism for control of plasma cortisol levels. Finally, plasma levels of injected, radioactive cortisol were decreased during stress, but recovered poststress, compared with baseline conditions, suggesting a stress-induced shift in cortisol compartmentalization ratios.
Biological Psychiatry, 2008
Background-Self-injurious behavior (SIB), a disorder that afflicts many individuals within both clinical and non-clinical populations, has been linked to states of heightened stress and arousal. However, there are no published longitudinal data on the relationship between increases in stress and changes in the incidence of SIB. The present study investigated the short-and long-term behavioral and neuroendocrine responses of SIB and control monkeys to the stress of relocation. Methods-Twenty adult male rhesus macaques were exposed to the stress of relocation to a new housing arrangement in a newly constructed facility. Daytime behavior, sleep, and multiple measures of hypothalamic-pituitary-adrenocortical (HPA) axis function were investigated before and after the move. Results-Relocation induced a complex pattern of short-and long-term effects in the animals. The SIB animals showed a long-lasting increase in self-biting behavior as well as evidence of sleep disturbance. Both groups exhibited elevated cortisol levels in saliva, serum, and hair, and also an unexpected delayed increase in circulating concentrations of corticosteroid binding globulin (CBG). Conclusions-Our results indicate that relocation is a significant stressor for rhesus macaques, and that this stressor triggers an increase in self-biting behavior as well as sleep disturbance in monkeys previously identified as suffering from SIB. These findings suggest that life stresses may similarly exacerbate SIB in humans with this disorder. The HPA axis results underscore the potential role of CBG in regulating long-term neuroendocrine responses to major stressors.
Neuropsychiatric disease and treatment, 2008
The present study compared the effects of direct and indirect stress on the behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in a two compartment box. In one compartment the direct stressed rat was subjected to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration). In the adjacent compartment, the indirect stressed rats witnessed the application of these electric foot shocks. Our data showed substantial behavioral changes in the open fi eld test, but limited effects in the elevated plus maze. The fi ndings suggested that single and repeated stress exposure may have different consequences, that the effects of stress exposure may develop over time and persist for an extended period, and that both direct and indirect stressed rats displayed a hyposensitive HPA axis following acute restraint stress. Overall our observations moderately indicate direct exposure to elicit behavioral changes, and both direct and indirect exposure to stress to result in aberrations within the neuroendocrine system. With additional development our stress models may be considered for studying the complex interrelationship between an external stressor, and the experience of the organism.
Reviews in the Neurosciences, 2008
Social non-human primates are potential animal models for studying changes in social dynamics because they build strong emotional bonds inside the group, much as do humans. The common marmoset, a small neotropical primate, is a suitable model because of its low maintenance cost and high reproductive output in captivity associated with the presence of affiliative relationships among the members of the social group and pair bond formation. The paradigm of involuntary separation is frequently used to study the physiological repercussions of ι social deprivation. In this review we point out ' the advantages of using social non-human primates as animal models for studying psychological disorders. We focused on New World primates, adding some original findings for common marmosets. Forty-eight adult individuals (24 females) were monitored over 25 days in two situations: baseline phase and separation phase. Variability in basal Cortisol levels was recorded for both males and females, and three types of Cortisol profile were drawn for the subjects in this population: high, medium and low. Basal Cortisol levels were a predictor of hormonal reactivity to social separation. The animals with low and high Cortisol levels were
Animal models of social stress: effects on behavior and brain neurochemical systems
Physiology & Behavior, 2001
Social interactions serve as an evolutionarily important source of stress, and one that is virtually ubiquitous among mammalian species. Animal models of social stress are varied, ranging from a focus on acute, intermittent, or chronic exposure involving agonistic behavior, to social isolation. The relative stressfulness of these experiences may depend on the species, sex, and age of the subjects, and subject sex also appears to influence the value of hypothalamic--pituitary--adrenal (HPA) axis activity as a general criterion for stress response: higher glucocorticoid levels are typically found in dominant females in some species. Social stress models often produce victorious and defeated, or dominant and subordinate, animals that may be compared to each other or to controls, but the appropriateness of specific types of comparisons and the interpretations of their differences may vary for the different models. Social stress strongly impacts behavior, generally reducing aggression and enhancing defensiveness, both inside and outside the stress situation. Social and sexual behaviors may be reduced in subordinate animals, as is activity and responsivity to normally rewarding events. However, some components of these changes may be dependent on the presence of a dominant, rather than representing a longer-term and general alteration in behavior. Social stress effects on brain neurotransmitter systems have been most extensively investigated, and most often found in serotonin and noradrenergic systems, with changes also reported for other monoamine and for peptidergic systems. Morphological changes and alterations of neogenesis and of cell survival particularly involving the hippocampus and dentate gyrus have been reported with severe social stress, as have longer-term changes in HPA axis functioning. These findings indicate that social stress models can provide high magnitude and appropriate stressors for research, but additionally suggest a need for caution in interpretation of the findings of these models and care in analysis of their underlying mechanisms.