The Dexamethasone Suppression Test as a Measure of Hypothalamic-Pituitary Feedback Sensitivity and its Relationship to Behavioral Arousal

Kalin, Ned H.; Cohen, Robert M.; Kraemer, Gary W.; Risch, S. Craig; Shelton, Steven E.; Cohen, M N; McKinney, William T.; Murphy, Dennis L.

doi:10.1159/000123137

Cited by 48 publications

(17 citation statements)

References 6 publications

(6 reference statements)

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“…in four divided doses starting immediately before heat stress, then every 6 h for 24 h. The dose of dexamethasone was based on a dose-response relationship established in rhesus monkeys, in which 0.5 mg/kg represents 30 times the cortisol suppressive dose (22). The control group received a vehicle consisting of NaPO 4 in a concentration similar to that of dexamethasone.…”

Section: Experimental Protocolmentioning

confidence: 99%

Glucocorticoids Do Not Protect Against the Lethal Effects of Experimental Heatstroke in Baboons

Bouchama¹,

Kwaasi²,

Dehbi³

et al. 2007

Shock

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The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.

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Section: Experimental Protocolmentioning

confidence: 99%

Glucocorticoids Do Not Protect Against the Lethal Effects of Experimental Heatstroke in Baboons

Bouchama¹,

Kwaasi²,

Dehbi³

et al. 2007

Shock

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“…We used a hormonal challenge protocol that permitted us to get an integrated picture of the squirrel's recent past while overriding the immediate stress response that the squirrel was experiencing because of the effects of capture and handling. This hormonal challenge protocol involved two steps: the dexamethasone suppression test (Kalin et al 1981) followed by the adrenocorticotropic hormone (ACTH) stimulation test. The dexamethasone suppression test is a method to assess whether the brain is registering glucocorticoid levels correctly and making the necessary negative feedback adjustment by reducing ACTH and cortisol production.…”

Section: Experimental Protocol and Predictionsmentioning

confidence: 99%

Reproduction at All Costs: The Adaptive Stress Response of Male Arctic Ground Squirrels

Boonstra

McColl

Karels

2001

Ecology

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Abstract. We tested the hypothesis that adult male arctic ground squirrels (Spermophilus parryii plesius) exhibit an adaptive stress response during the mating period that may compromise their survival, whereas males at other times (nonreproductive adult males and juvenile males) have a normal functional stress response. We assessed the physiological responsiveness of the stress axis, of energy mobilization, and of the immune response by subjecting adult breeding males, adult nonbreeding males, and juvenile males to a hormonal challenge and an immunocompetence challenge. At the onset of the breeding season in spring, only 25-30% of the population were males, and of those present during the mating period, half disappeared soon thereafter, and 82% were not replaced by immigrants. Adult breeding males had the highest levels of free cortisol, the lowest maximum corticosteroidbinding capacity, slight dexamethasone resistance, the lowest hematocrit, the lowest number of white blood cells, the highest number of eosinophils, and the poorest ability to respond to the foreign antigen challenge in comparison with the other two male classes. All of these characteristics were indicative of chronic stress in breeding males that may directly compromise their survival. Juvenile males in mid-August also showed many, but not all of these characteristics, indicative of a prolonged period of stress, presumably associated with the period of dispersal. Testosterone levels remained high irrespective of age or breeding condition, decreased when dexamethasone was injected, and increased when ACTH was injected. These latter results are unique in mammals. High testosterone levels and their augmentation with stressors may play a key role in maintenance of aggressive behavior. We conclude that breeding male arctic ground squirrels exhibit an adaptive stress response in which they trade off survival for reproduction. We hypothesize that similar stress responses may have evolved in other species with comparable life histories.

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“…In primates, reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and, in particular, negative feedback sensitivity or adrenal responsiveness measured after dexamethasone or ACTH administration, are taken as measures of stress reactivity [Kalin et al, 1981]. Several studies have examined how individual differences in these measures are related to social status Sapolsky et al, 1997;Shively et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation

et al. 2000

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The purpose of the present study was to determine whether various behavioral and hormonal markers obtained in individually housed monkeys would be predictive of social rank following group housing. Body weight, serum cortisol and testosterone levels, and locomotor activity in an open‐field apparatus were examined in 20 experimentally naive male cynomolgus monkeys (Macaca fascicularis) while they were individually housed. It was hypothesized that eventual subordinate monkeys would have higher cortisol levels and increased locomotor activity scores. These monkeys were then placed in social groups of four (five pens of four monkeys), and social rank was determined based on outcomes of dyadic agonistic encounters. Body weight correlated significantly with eventual social rank. In general, the heavier the monkey the higher the social rank. Locomotor activity in an open‐field apparatus following administration of a low dose of cocaine (0.01 mg/kg, i.v.), which has been shown to increase CNS dopamine, correlated with eventual social rank such that individually housed monkeys with high levels of locomotion were more likely to become subordinate. Serum cortisol and testosterone levels failed to correlate with eventual social rank. Hypothalamic‐pituitary feedback sensitivity and adrenal responsiveness were examined by measuring cortisol levels after administration of dexamethasone and following ACTH challenge. Cortisol responses in these tests were not associated with eventual social rank. These results suggest that, in addition to body weight, the level of reactivity in a novel environment after administration of a low dose of cocaine is a potential trait marker for social rank. This trait is apparently not associated with hormone levels, but may involve other CNS mechanisms. Am. J. Primatol. 52:115–131, 2000. © 2000 Wiley‐Liss, Inc.

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The Dexamethasone Suppression Test as a Measure of Hypothalamic-Pituitary Feedback Sensitivity and its Relationship to Behavioral Arousal

Cited by 48 publications

References 6 publications

Glucocorticoids Do Not Protect Against the Lethal Effects of Experimental Heatstroke in Baboons

Glucocorticoids Do Not Protect Against the Lethal Effects of Experimental Heatstroke in Baboons

Reproduction at All Costs: The Adaptive Stress Response of Male Arctic Ground Squirrels

Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation

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