Adrenocortical Activation Research Articles

Social and sexual behaviors predict immune system activation, but not adrenocortical activation, in male rhesus macaques

Social and sexual behaviors predict immune system activation, but not adrenocortical activation, in male rhesus macaques

Microscopic features of the rat adrenal gland associated with chronic codeine phosphate administration.

Codeine is an opioid analgesic and antitussive that has been widely abused. Some adverse effects noted with its abuse include adrenocortical insufficiency and activation of the hypothalamic-pituitary-adrenal axis. The structural basis for these dysfunctions is not clearly understood. Twenty-five adult male rats were used for the study. They were divided into intervention and control groups that were administered 40 mg/kg of codeine phosphate and normal saline respectively by gavage daily for 50 days. Subsequently, both groups were given normal saline for a further fourteen days to note recovery changes. At day 0, 50 and 64, rats were randomly selected from both groups, euthanized and adrenal glands harvested for histological processing and analysis. At day 50 of codeine administration, the adrenal glands demonstrated an increase in zona fasciculata thickness but a decrease in zona reticularis thickness. Lower values were noted in the volume density of zona reticularis and cells count of the medulla in the experimental compared to the control groups (P-value<0.05). The experimental group also showed an increase in vascularization and connective tissue in the glands. After 14 days of recovery, most of the changes observed in experimental animals were reversed and the adrenal glands in both groups had similar features. A decrease in cell count of the adrenal medulla was however observed (P-value<0.05). In conclusion administration of codeine phosphate causes discernible changes in the microscopic structure of the adrenal gland, most of which appear to be reversed after two weeks recovery period.

Transport-related stress in five-day-old foals and their dams

Horses are frequently transported by road but little is known about the stress response of transported newborn foals. In this study, we have analyzed the stress response of postpartum Haflinger mares (n = 6 over two years) and their 5-day-old foals (n = 12) to a 20 km road transport in a trailer with the middle partition either removed or separating the mare and her foal. Noninvasive techniques were used to analyze the physiological stress variables such as salivary cortisol, heart rate, and heart rate variability (HRV). Mares and their foals responded to transport with an increase in cortisol concentration (P < 0.001). The increase was more pronounced and prolonged in foals compared to their mothers (P = 0.001). Heart rate increased in mares and foals during transport (P < 0.001) but this increase was less pronounced in foals compared to mares (P = 0.001). The HRV increased during transport (P < 0.05) in mares but remained constant in transported foals. The presence or absence of the partition was largely without effect on the physiological stress variables determined. In conclusion, 5-day-old foals respond to road transport with a clear adrenocortical activation which was more pronounced than in their dams. There were no changes of HRV in transported foals.

Faecal cortisol metabolites as an indicator of adrenocortical activity in farmed silver foxes (Vulpes vulpes)

Measuring glucocorticoid metabolites in faeces has proven a useful, non-invasive method to monitor adrenocortical activity in several farm and wild species. Unlike plasma cortisol, whose sampling requires restraint and blood draws, faecal cortisol metabolites (FCM) may be particularly suitable for farmed silver foxes as these animals are sensitive to handling by humans. Prior to using FCM as a potential indicator of stress in silver foxes, however, a proper physiological and/or biological validation is required. Here, we determined FCM concentrations in 30 silver foxes (10 adult vixens, 10 juvenile females and 10 juvenile males) every alternate hour for 24h after 1) an increase in cortisol induced by injection with synthetic ACTH (hereafter ACTH), and 2) a 2min period of handling and restraint. Baseline FCM values, recorded every fourth hour for 24h before the ACTH and handling treatments, served as controls. FCM values increased significantly following ACTH injection (P=0.0001) and handling (P<0.0001). The time to reach peak FCM concentrations after ACTH injection tended to differ between groups (P=0.055) averaging (±SE) 11.0±1.04, 10.6±1.30 and 7.8±0.20h for vixens, juvenile females and juvenile males, respectively. After handling, peak FCM values were reached after 10.1±0.55h with no significant differences between groups. Peak concentrations averaged 2143±264ng/g after the ACTH and 1008±128ng/g after handling, compared to 475±48ng/g for baseline levels. Peak FCM values tended to vary between individuals more in females than in males. Baseline FCM concentrations prior to handling were, unexpectedly, higher in more confident foxes (P=0.004), a finding perhaps indicating a potential preparative role of cortisol in silver foxes. There was also a negative trend between foxes’ confidence and their times to reach peak FCM concentrations after handling (P=0.062), suggestive of a prolonged adrenocortical activation in more fearful individuals. Based on the rates that foxes produce faecal samples and the times to reach maximum FCM concentrations, we suggest a four hour delay to first faeces collection, before collecting samples every third hour the next 12 following hours to monitor elevations after an acute stressor. Our study confirms faecal cortisol metabolites as a valid indicator of adrenocortical activity in farmed silver foxes.

The adaptive calibration model of stress responsivity: An empirical test in the Tracking Adolescents' Individual Lives Survey study.

The adaptive calibration model (ACM) is a theory of developmental programing focusing on calibration of stress response systems and associated life history strategies to local environmental conditions. In this article, we tested some key predictions of the ACM in a longitudinal study of Dutch adolescent males (11-16 years old; N = 351). Measures of sympathetic, parasympathetic, and adrenocortical activation, reactivity to, and recovery from social-evaluative stress validated the four-pattern taxonomy of the ACM via latent profile analysis, though with some deviations from expected patterns. The physiological profiles generally showed predicted associations with antecedent measures of familial and ecological conditions and life stress; as expected, high- and low-responsivity patterns were found under both low-stress and high-stress family conditions. The four patterns were also differentially associated with aggressive/rule-breaking behavior and withdrawn/depressed behavior. This study provides measured support for key predictions of the ACM and highlights important empirical issues and methodological challenges for future research.

Correction: Radley et al., The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

Correction: Radley et al., The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation.

Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic cocaine self-administration in rats leads to decrements in medial prefrontal structural and functional plasticity. Notably, these impairments were largely accounted for in rats that self-administered cocaine compared with yoked counterparts. Moreover, we verified previous reports showing that adrenocortical output is augmented by cocaine administration and is more protracted in rats that were permitted to receive the drug contingently instead of passively. These studies suggest that increased adrenocortical activity resulting from cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity.

Differences in prefrontal cortex GABA/glutamate ratio after acute restraint stress in rats are associated with specific behavioral and neurobiological patterns

In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary–adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by 1H high-resolution magic angle spinning magnetic resonance spectroscopy (1H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed in the stressed animals may participate in shaping individual differences in psychophysiological reactions.

Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food: Role of the Central Amygdala

The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB(1)) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and the CB(1) receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB(1) receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data show that (i) the 2-AG-CB(1) receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB(1) receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity.

Maternal exposure to low levels of corticosterone during lactation increases social play behavior in rat adolescent offspring

Although costly in energy and time, social play is present and evolutionarily conserved in nearly all young mammals. Ontogenetic factors responsible for this particular form of supposed rewarding behavior are incompletely understood. Here, we have focused our attention on maternal glucocorticoid hormone. We used a model in which neonate rats are fed by mothers in which drinking water has been supplemented with 0.2 mg/ml corticosterone. The control groups were lactated by water-drinking mothers. Both male and female adolescent offspring of corticosterone (CORT) supplemented dams (CORT-nursed) showed an increase in social play behavior (i.e., pinning, pouncing, wrestling/boxing and social exploration) when compared to controls. No differences were observed between CORT-nursed progeny of both sexes and controls in the exploration of the arena during the social encounter. Finally, no differences were found in CORT plasma levels in basal conditions and following a social play session in both male and female CORT-nursed rats. These results indicate that variations in the maternal glucocorticoid status are able, directly or indirectly, to influence social play behavior in the offspring, although there is no direct relationship between the level of social play behavior and the intensity of adrenocortical activation.

Kindergarten stressors and cumulative adrenocortical activation: The “first straws” of allostatic load?

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Quality of early family relationships and the timing and tempo of puberty: effects depend on biological sensitivity to context.

Guided by evolutionary-developmental theories of biological sensitivity to context and reproductive development, the current research examined the interactive effects of early family environments and psychobiologic reactivity to stress on the subsequent timing and tempo of puberty. As predicted by the theory, among children displaying heightened biological sensitivity to context (i.e., higher stress reactivity), higher quality parent-child relationships forecast slower initial pubertal tempo and later pubertal timing, whereas lower quality parent-child relationships forecast the opposite pattern. No such effects emerged among less context-sensitive children. Whereas sympathetic nervous system reactivity moderated the effects of parent-child relationships on both breast/genital and pubic hair development, adrenocortical activation only moderated the effect on pubic hair development. The current results build on previous research documenting what family contexts predict variation in pubertal timing by demonstrating for whom those contexts matter. In addition, the authors advance a new methodological approach for assessing pubertal tempo using piecewise growth curve analysis.

“Green odor” inhalation by rats down-regulates stress-induced increases in Fos expression in stress-related forebrain regions

In the present study, on rats, a quantitative analysis of Fos protein immunohistochemistry was performed as a way of investigating the effects of inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) on the neuronal activations in stress-related forebrain regions induced by acute and repeated stress. Rats were exposed to restraint stress for 90 min each day for 1, 2, 4, 7, or 11 consecutive days. The hypothalamic paraventricular nucleus (PVN), amygdala, hippocampus and paraventricular thalamic nucleus (PVT) were examined. Both acute and repeated restraint stress increased Fos-positive cells in the entire hypothalamic PVN, in the central and medial amygdala, and in PVT, although these responses declined upon repeated exposure to such stress. The stress-induced Fos responses were much weaker in rats that inhaled green odor during each day's restraint. No increases in Fos-positive cells were observed in the hippocampus in acutely stressed rats. The Fos-immunoreactive response to acute stress shown by the piriform cortex did not differ significantly between the vehicle + stress and green + stress groups. Green odor had inhibitory effects on the stress-induced corticosterone response, body-weight loss, and adrenal hypertrophy. These results suggest that in rats, green odor inhalation may, in an as yet unknown way, act on the brain to suppress activity in the neuronal networks involved in stress-related responses (such as activation of the hypothalamo–pituitary–adrenocortical axis and activation of the sympathetic nervous system, as well as stress-induced fear responses).

Working memory performance after acute exposure to the cold pressor stress in healthy volunteers

Effects of acute stress exposure on learning and memory have been frequently studied in both animals and humans. However, only a few studies have focused specifically on working memory performance and the available data are equivocal. The present study examined working memory performance during the Sternberg item recognition task after exposure to a predominantly adrenergic stressor. Twenty four healthy subjects were randomly assigned to a stress group or a control group. The stress group was exposed to the cold pressor stress test (CPS; i.e. insertion of the dominant hand into ice water for 60s), while 37 °C warm water was used with the control group. Twenty minutes after the stress exposure, working memory performance was tested with the Sternberg item recognition task with three levels of cognitive load. Sympathetic nervous system and hypothalamic pituitary adrenocortical (HPA) axis activation during CPS, were assessed by measuring heart rate and salivary cortisol before and during (heart rate) or 30 min after (cortisol) the stress procedure. Exposure to the CPS test was associated with a significant increase in heart rate but no increase in salivary cortisol. Participants exposed to the stress procedure showed significantly shorter reaction times during trials with higher cognitive load but tended to show higher false alarm rates than control subjects. The present results indicate that exposure to CPS can be associated with signs of both enhanced and impaired working memory performance. The observed behavioral pattern might represent a form of streamlined information processing advantageous in a threatening situation.

Fear Responses of Offspring from Divergent Quail Stress Response Line Hens Treated with Corticosterone During Egg Formation

Increased fearfulness has been associated with adrenocortical activation. Maternal corticosterone (B) treatment increases egg B, and elevated B in ovo enhances chick avoidance of humans. Quail selected for exaggerated (high stress, HS) rather than reduced (low stress, LS) plasma B response to stress are more fearful, and more B is found in HS hen eggs. Thus, we used tonic immobility (TI) and hole-in-the-wall box (HWB) emergence tests to assess fear in chicks hatched from eggs of LS and HS hens implanted with B or no B (CON). The number of inductions required to attain TI, latency to first alert head movement, and duration of TI were determined in one study and the latency until first vocalization (LATVOC), numbers of vocalizations (VOCS), proportions of chicks vocalizing, and the latencies to head (HE) and full-body (FE) emergence from a HWB were assessed in another. The LS chicks required less inductions (P < 0.0005) and had shorter latency to first alert head movement (P < 0.02) than HS chicks, although the duration of TI was unaffected by any of the treatments. During the acclimation period of the HWB tests, more (proportions of chicks vocalizing; P < 0.0001) HS chicks alarm-called sooner (LATVOC; P < 0.0001) and more often (VOCS; P < 0.0001) than did LS chicks, and, although maternal implant treatment did not affect LATVOC, progeny of B-implanted hens showed a tendency toward less (P < 0.07) VOCS than the CON. Chicks hatched from eggs of B-implant mothers also took longer to achieve HE (P < 0.06) and FE (P < 0.05) from the HWB than did their CON counterparts. Stress line, implantation treatment, and their interaction did not alter HE or FE responses. The data suggest that quail stress line genome may or may not be affecting certain fear and alarm responses in chicks via the same mechanism(s) that underlies how elevating maternal B increases egg levels of B that in turn alters the fear behavior of progeny.

Infection as a stressor: a cytokine-mediated activation of the hypothalamo-pituitary-adrenal axis?

Infections are associated with increased plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone. Hypothalamo-pituitary-adrenal (HPA) responses have also been observed with immunological stimuli that are not infective. Although such responses have been suggested to be mediated by ACTH secreted by lymphocytes, adrenocortical activation by immunological stimuli requires a functional pituitary. The most likely mechanism by which immunological stimuli activate the HPA axis involves production of cytokines by lymphocytes. The prime candidate is interleukin 1 (IL-1), because IL-1 production follows activation of the immune system and IL-1 administration is a potent activator of the HPA axis. However, other cytokines, such as tumour necrosis factor, may also be involved. Most immunological stimuli and IL-1 also activate both peripheral and central noradrenergic neurons. IL-1-induced activation of the HPA axis in vivo depends upon secretion of corticotropin-releasing factor (CRF), an intact pituitary, and the ventral noradrenergic bundle which innervates the CRF-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Besides elevating body temperature, administration of IL-1 elicits a number of behavioural responses in rats and mice, including anorexia, increased sleep time, decreased investigation of novel objects and other animals, increased defensive withdrawal and other behaviours characteristic of sickness. Some of these responses can be reversed by CRF-antagonists and mimicked by CRF administration. Thus, endogenous production of IL-1 can account for a range of physiological and behavioural responses characteristic of sickness. Nevertheless, definitive evidence that IL-1 mediates these responses in sick animals is lacking.

Immediate-early genes and the neural bases of photic and non-photic entrainment.

The expression of immediate-early genes (IEGs) within the mammalian suprachiasmatic nucleus (SCN) identifies individual light-responsive cells of the circadian system. Cells immunoreactive for products of IEGs form a neurochemically heterogeneous population, of which a few are VIP (vasoactive intestinal peptide)-immunoreactive or GRP (gastrin-releasing peptide)-immunoreactive, although the phenotypes of most of the others have yet to be determined. Dual-labelling experiments with anatomical tracers reveal that only a minority of efferent projection neurons of the SCN are immunoreactive for IEG products, and it is likely that the majority of the immunoreactive cells are interneurons or glia. Photic induction of IEGs is mediated via NMDA (N-methyl-D-aspartate) and non-NMDA glutamatergic receptors, the SCN expressing a topographically specific complement of subtypes of the NMDA receptor. Non-photic cues (arousal) can shift the clock but this is not associated with expression of IEGs, demonstrating that the proteins encoded by IEGs are probably involved in transducing photic cues, rather than shifting the clock per se. Their induction provides an anatomically explicit marker for circadian phase and photic sensitivity and so is useful in analyses of circadian function, for example, in the tau mutant hamster. Non-photic phase shifts are accompanied by adrenocortical activation, confirming the importance of arousal in shifting of the clock. The phase-shifting effect of arousal can be blocked by treatment with the serotonin receptor antagonist ketanserin, suggesting that ascending serotonergic input to the forebrain, possibly directly to the SCN, is an important mediator of entrainment by arousal.

Relationship between self-reported mental stressors at the workplace and salivary cortisol

To investigate the association between work stress measures and salivary cortisol excretion in working and weekend days. In a sample of 68 healthy young call-centre operators dimensions of job stress from the demand-control model were related to repeated measures of salivary cortisol on seven samples (at awakening, +30 min, +60 min, + 3 h, +6 h, +9 h, and +12 h after awakening) at two working days and a weekend day. The cortisol excretion on work days was higher than during weekend day with gender-specific differences as women only showed higher significant values for area under the curve (AUC(G)) and Diurnal cycle (chi(2) (2) = 8.10, P < 0.05; chi(2) (2) = 15.75, P < 0.05, respectively). There were no associations between job demand, job control and cortisol excretion, while the sociodemographic characteristics of the call-centre operators showed linear relation with the diurnal pattern of cortisol secretory activity. The hypothalamic-pituitary adrenocortical axis activation was higher in working day than in weekend day. This activation measured by salivary cortisol was not related to self-reported mental stressors assessed with job strain model. The availability of more specific psychometric scales would be useful to explore the relationship between salivary cortisol levels and measures of mental stress at workplace.

Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression

Several lines of evidence implicate the pro-inflammatory cytokine interleukin-1 (IL-1) in the etiology and pathophysiology of major depression. To explore the role of IL-1 in chronic stress-induced depression and some of its underlying biological mechanisms, we used the chronic mild stress (CMS) model of depression. Mice subjected to CMS for 5 weeks exhibited depressive-like symptoms, including decreased sucrose preference, reduced social exploration and adrenocortical activation, concomitantly with increased IL-1 beta levels in the hippocampus. In contrast, mice with deletion of the IL-1 receptor type I (IL-1rKO) or mice with transgenic, brain-restricted overexpression of IL-1 receptor antagonist did not display CMS-induced behavioral or neuroendocrine changes. Similarly, whereas in wild-type (WT) mice CMS significantly reduced hippocampal neurogenesis, measured by incorporation of bromodeoxyuridine (BrdU) and by doublecortin immunohistochemistry, no such decrease was observed IL-1rKO mice. The blunting of the adrenocortical activation in IL-1rKO mice may play a causal role in their resistance to depression, because removal of endogenous glucocorticoids by adrenalectomy also abolished the depressive-like effects of CMS, whereas chronic administration of corticosterone for 4 weeks produced depressive symptoms and reduced neurogenesis in both WT and IL-1rKO mice. The effects of CMS on both behavioral depression and neurogenesis could be mimicked by exogenous subcutaneous administration of IL-1 beta via osmotic minipumps for 4 weeks. These findings indicate that elevation in brain IL-1 levels, which characterizes many medical conditions, is both necessary and sufficient for producing the high incidence of depression found in these conditions. Thus, procedures aimed at reducing brain IL-1 levels may have potent antidepressive actions.

Decreased heat tolerance is associated with hypothalamo–pituitary–adrenocortical axis impairment

When rats are exposed to heat, they adapt themselves to the stressor with a wide inter-individual variability. Such differences in heat tolerance may be related to particularities in the hypothalamo–pituitary–adrenocortical (HPA) axis activation. To further this hypothesis, 80 rats instrumented with a telemetric device for abdominal temperature (T abd) measurement were separated into two groups. Sixty-eight rats were exposed during 90 min at an ambient temperature of 40 °C, and 12 rats to an ambient temperature of 22 °C. Heat-exposed rats were then divided into three groups using the a posteriori k-means clustering method according to their T abd level at the end of heat exposure. Heat tolerant rats (Tol, n=30) exhibiting the lowest T abd showed a slight dehydration, a moderate triglyceride mobilization, but the highest plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels. Conversely, heat exhausted rats (HE, n=14) presented the highest T abd, a higher degree of dehydration, a greater metabolic imbalance with the lowest plasma triglyceride level and the highest lactate concentration, as well as a lowest plasma corticosterone and ACTH levels. The fact that the proopiomelanocortin (POMC) mRNA content within the pituitary was low despite of a high c-fos mRNA level is also relevant. Current inflammatory processes in HE rats were underlined by lower inhibitory factor κBα (IκBα) mRNA and higher tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA. In conclusion, data show that intolerance to heat exposure is associated to an HPA axis impairment, possibly related to changes occurring in the IκBα and TNF-α mRNA levels.