Plasma Corticosterone Concentrations Research Articles

Stress response to handling is short lived but may reflect personalities in a wild, Critically Endangered tortoise species.

We investigated the acute stress response associated with animal personalities by measuring plasma glucocorticoids throughout handling and collected ~2 years of movement and behavioural data in a wild, Critically Endangered animal, Astrochelys radiata (radiated tortoise). To determine whether our standard, brief conscientious handling procedures induce a stress response in our target species, we applied a stressor by way of initial animal processing and deployment of telemetry equipment. During surveys and processing, we sampled animals immediately upon detection, again after completing transmitter attachment and processing, and a final time the following day. We then used radiotelemetry to follow a subset of the animals for 22 months while collecting behavioural, climatic and location data. We found that brief and conscientious handling did not illicit consistent changes in plasma concentrations of the stress hormone corticosterone (CORT) but did reveal tremendous individual variation in response. The CORT concentration ranged more than 200-fold after imposing the stressor and returned to near-baseline values by the following day. When we accounted for the wide variation by calculating the degree of each individual's stress response relative to its baseline over its processing time, we discovered two non-overlapping physiological response types; those in which CORT concentrations increased dramatically in response to handling (219±89.8 pg/ml/min) and those in which CORT varied only slightly (5.3±8.9 pg/ml/min). The response types (strong vs. mild) also predicted body condition, home range size, activity, and behavioural tendencies. The degree of the individual's stress response in this species may be one component of correlated physiological and behavioural traits (animal personalities), which have previously been obscured in other chelonian studies by the use of mean values and should be considered in future conservation management applications for chelonian species.

The effects of electrical stunning voltage on meat quality, plasma parameters, and protein solubility of broiler breast meat

This study was designed to compare the effects of different stunning voltages of pulsed direct current on meat quality of broilers. For this purpose, plasma parameters, blood loss, carcass damage, and meat water holding capacity, color, shear force, pH, and protein solubility were analyzed. A total of 400 broilers were divided into 5 treatment groups and stunned with 5, 15, 25, 35, and 45 V at 750 Hz and 10 s, respectively. Blood samples were collected immediately after cutting the neck. Pectoralis major muscles were removed from the carcass after chilling and placed on ice. Breast muscle pH and meat color were determined at both 2 and 24 h postmortem. Dripping loss, cooking loss, pressing loss, and cooked breast meat shear values were determined after 24 h postmortem. The 5 V treatment significantly increased (P < 0.05) blood plasma corticosterone and lactate concentration compared with the other groups. The carcass damage of wings, Pectoralis major, and Pectoralis minor was significant in the 5, 35, and 45 V groups. The pH of 2 h postmortem in the 5 and 45 V groups was significantly lower (P < 0.05) than in the 15 and 25 V groups. In the 5 and 45 V groups, the protein solubility and shear force value were significantly lower (P < 0.05) and dripping loss was significantly higher (P < 0.05) than the other groups.

Effects of Moderate Food Deprivation on Plasma Corticosterone and Blood Metabolites in Common Watersnakes (Nerodia sipedon)

Abstract Lack of food is one of the most common natural stressors that animals face, yet the physiological response to food restriction in most nonmammalian species is poorly understood. Food restriction can elicit an elevation of plasma glucocorticoid hormones and changes in blood metabolites in several vertebrates, but this has not been shown in snakes, despite their remarkable ability to tolerate food shortages. The purpose of this study was to determine the physiological response to moderate food deprivation in Common Watersnakes (Nerodia sipedon). When food was withheld for 15 d, snakes lost body mass, had elevated baseline plasma corticosterone concentrations, lower hematocrit, and depressed levels of triglycerides and uric acid. Food deprivation had no effect on blood glucose or lactate. Elevation of corticosterone levels could help snakes mobilize stored energy to allow them to survive periods of restricted feeding. Depressed triglycerides likely indicate increased utilization of lipid stores. Bec...

Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring

BackgroundThe mother’s consumption of high-fat food can affect glucose metabolism and the hypothalamic–pituitary–adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring.MethodsFemale rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers’ diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels.ResultsAccording to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group.ConclusionMothers’ high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

Postnatal Light Effects on Pup Stress Axis Development Are Independent of Maternal Behavior.

Postnatal environment shapes brain development during key critical periods. We have recently found that postnatal light environment has long-term effects on the stress and circadian systems, which can lead to altered stress responses, circadian behavior and a depressive phenotype in adulthood. However, it is still unclear how light experience affects the postnatal development of specific stress markers in the pup brain and the role played by maternal behavior and stress. To test this, we raised mice under either light-dark cycles (LD), constant light (LL) or constant darkness (DD) during the suckling stage. After weaning, all mice were exposed to LD until adulthood. Results show that postnatal light environment does not have any significant effects on dam stress levels (plasma corticosterone concentration, Arginine-vasopressin and Glucocorticoid receptor (GR) protein expression in the brain) or maternal behavior, including licking and grooming. Light environment does not have a major effect on litter characteristics or pup growth either. Interestingly, light environment during the suckling stage significantly impacted Corticotrophin-releasing hormone (CRH) and Gr mRNA expression in pup brain during development. Furthermore, a difference in Crh mRNA expression between LL- and DD-raised mice was still observed in adulthood, long after the exposure to abnormal light environments had stopped. Taken together, these data suggest that the long-term effects of postnatal light environment on the pups' stress system cannot be attributed to alterations in either maternal behavior and/or stress axis function. Instead, postnatal light experience may act directly on the pup stress axis and/or indirectly via circadian system alterations.

Heat exposure alters the mRNA expression of growth- and stress-related genes in chicks

High ambient temperature, a major stressor, impairs the growth of chickens. In this study, we examined the effect of heat exposure on the mRNA expression of various growth related genes, such as growth hormone (GH), insulin-like growth factor-1 (IGF1), GH-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), and somatostatin (SST) in layer-type chickens (Gallus gallus domesticus) at an early age. In addition, we examined the reactivity of the corticotrophin-releasing hormone (CRH) system, one of the stress-regulating pathways, to heat exposure and its role in altering the growth related genes. Four-day heat exposure reduced the body weight gain, feed intake, and feeding efficiency and increased the rectal temperature of chicks (P<0.05). The mRNA expression levels of pituitary GH, liver IGF1, and diencephalic GHRH decreased with heat exposure (P<0.05) whereas the levels of TRH or SST did not change. Heat exposure also reduced the diencephalic mRNA expression level of CRH and increased pituitary CRH receptor-2 mRNA and the plasma corticosterone (CORT) concentration (P<0.05), suggesting that heat exposure affected the hypothamic-pituitary adrenal gland (HPA) axis. Similar to the heat-exposure study, subcutaneous injection of CORT for 4 days decreased body weight, and the mRNA expression of pituitary GH and liver IGF1 (P<0.05). The present study demonstrated that heat exposure reduced the mRNA expressions of pituitary GH and liver IGF1, and suggested that the change in mRNA expression may have been partly caused by CORT.

Maternal occlusal disharmony during pregnancy induces spatial memory deficits associated with the suppression of hippocampal neurogenesis in adult mouse offspring

Background and objectiveMaternal stress during pregnancy is an important factor affecting fetal brain development and leading to behavioral disorders such as spatial learning deficits and inhibition of hippocampal neurogenesis in the offspring. Occlusal disharmony induces cognitive deficits by suppressing hippocampal neurogenesis via increased plasma corticosterone levels. The present study aimed to explore the effects of maternal occlusal disharmony during pregnancy on hippocampal morphology and function in the adult mouse offspring. DesignOcclusal disharmony was induced in pregnant mice during the last week of gestation. Male offspring were raised until 4 months old, and then the Morris water maze was performed as a spatial memory test. Newborn cell proliferation in the hippocampal dentate gyrus was analyzed using 5-bromodeoxyuridine (BrdU) immunohistochemical method in separate groups of mice. ResultsPlasma corticosterone concentrations were significantly higher in dam with occlusal disharmony. In the adult offspring, maternal occlusal disharmony not only induced learning deficits, but also suppressed cell proliferation in the hippocampal dentate gyrus compared with control mice. ConclusionThese findings suggest that maternal occlusal disharmony during pregnancy increases plasma corticosterone concentrations in the dam, which leads to learning deficits and suppression of hippocampal cell proliferation in the offspring. Occlusal disharmony in the dam may be a risk factor for cognitive impairment in the offspring.

Higher susceptibility of somatostatin 4 receptor gene-deleted mice to chronic stress-induced behavioral and neuroendocrine alterations

The somatostatin 4 receptor (sst4) is widely expressed in stress-related brain areas (e.g. hippocampus, amygdala) and regulates the emotional behavior in acute situations. Since its importance in chronic stress-induced complex pathophysiological alterations is unknown, we investigated the involvement of sst4 in the responsiveness to chronic variable stress (CVS). Sstr4 gene-deficient (Sstr4−/−) mice and their wildtype counterparts (Sstr4+/+) were used to examine the behavioral and neuroendocrine alterations as well as chronic neuronal activity (FosB expression) changes in response to CVS. In Sstr4+/+ mice, there was no behavioral response to the applied CVS paradigm. In contrast, immobility time in the tail suspension test increased after the CVS in the knockouts. In the forced swim test, Sstr4−/− animals showed increased baseline immobility and then it decreased after the CVS. Light–dark box and open field test behaviors and sucrose preference did not respond to the stress in the knockouts. Adrenal weights increased and thymus weights decreased in both Sstr4+/+ and Sstr4−/− mice demonstrating the effect of chronic stress. The relative adrenal weight of stressed knockouts increased to a greater extent, while relative thymus and body weights decreased only in the Sstr4−/− mice. Basal plasma corticosterone concentrations did not change after the CVS in either genotype. FosB immunopositivity in the central and basolateral amygdaloid nuclei was enhanced in stressed knockouts, but not in wild types. This is the first evidence that sst4 activation is involved in the behavioral and neuroendocrine alterations induced by chronic stress with a crucial role of plastic changes in the amygdala.

Functional evidence that the nucleus of the hippocampal commissure shows an earlier activation from a stressor than the paraventricular nucleus: Implication of an additional structural component of the avian hypothalamo-pituitary-adrenal axis

Despite extensive data addressing the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in vertebrates, the neuroendocrine regulation of stress in birds remains incomplete. The paraventricular nucleus (PVN) contains the key neuropeptides, corticotropin releasing hormone (CRH) and arginine vasotocin (AVT), containing neurons. However, another population of CRH neurons was recently identified in a septal nucleus called the nucleus of the hippocampal commissure (NHpC). Therefore, the current study investigated changes in gene expression of CRH and AVT in the PVN and CRH in the NHpC, as well as changes in plasma corticosterone concentrations following a stressor, food deprivation. In the NHpC, a rapid increase in CRH mRNA levels was observed as early as 2h, while relative CRH mRNA expression in the PVN increased thereafter from 4 to 12h of food deprivation. On the other hand, relative mRNA levels of AVT in the PVN were not observed until 8h and significantly increased at 12 and 24h following food deprivation. Furthermore, at the level of the anterior pituitary, relative expression of proopiomelanocortin transcripts followed gene expression patterns of CRH and AVT in the brain. In the absence of food, the pattern of plasma CORT showed an initial rise at 2h and a fourfold increase was measured at 4h that was sustained through 24h. Taken together, results from this study suggest that (1) CRH neurons in the NHpC appear to be the first responsive neurons to stress stimuli compared to those in the PVN, (2) CRH is predominantly functional in the early phase of stress while AVT is involved in the later phase of the stress period and (3) in birds, CRH neurons in the NHpC appear to be part of the classical HPA axis.

CRF1 receptor-deficiency increases cocaine reward

Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity.

Mechanism for leptin's acute insulin-independent effect to reverse diabetic ketoacidosis.

The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis. Similarly, adrenalectomized type 1 diabetic (T1D) rats exhibited decreased rates of lipolysis, HGP, and ketogenesis; these effects were reversed by corticosterone infusion. Leptin-induced decreases in lipolysis, HGP, and ketogenesis in DKA were also nullified by relatively small increases (15 to 70 pM) in plasma insulin concentrations. In contrast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled T1D was associated with decreased food intake, reduced plasma glucagon and corticosterone concentrations, and decreased ectopic lipid (triacylglycerol/diacylglycerol) content in liver and muscle. Collectively, these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D.

Alterations in VEGF expression induced by antidepressant drugs in female rats under chronic social stress.

Vascular endothelial growth factor (VEGF) is thought to serve a role in neurogenesis and the stress response. Although a definite link between the action of antidepressants and VEGF has not been identified, it is assumed that VEGF, as a neurotrophic factor, serves an important role in the effects of antidepressant treatment. To examine this, the present study subjected adult female rats to four weeks of social instability stress and measured the effect of antidepressant treatment on the expression of VEGF. Firstly, endocrine markers of stress and body weight were measured in parallel with behavioral tests prior to and following subjection to stress. Then, the effect of 28-day daily treatment with desipramine (DMI; 10 mg/kg), fluoxetine (5 mg/kg) or tianeptine (10 mg/kg) on the number of copies of VEGF mRNA in the amygdala, hippocampus and hypothalamus, and on serum VEGF protein levels, of rats subjected to chronic stress was determined. In addition, the weight of the adrenal glands was measured following subjection to stress. Exposure to chronic stress was found to increase the rats' sucrose preference, and diminish their tendency for general exploration and time spent in the open. The relative adrenal weights of the stressed rats were significantly increased compared with the control. Plasma concentrations of corticosterone and adrenocorticotropic hormone were not significantly augmented. In addition, the present study identified that stress elevated VEGF mRNA expression in all studied neural structures. Furthermore, the results identified that the stress-induced increase in VEGF mRNA expression in the amygdala and hypothalamus was attenuated by long-term administration of DMI. Conversely, a decrease in serum VEGF concentration was observed in stressed rats, which was not reversed by treatment with antidepressants. In conclusion, the current study suggests that under conditions of stress, VEGF serves a role in the mechanism of action of DMI, through modulating activity of the norepinephrine system.

Interpopulation variability of endocrine and metabolic response to cold stress in northern red-backed vole (Myodes rutilus)

In natural environment, stresses, when animals happen to be exposed to them, influence the functional activity of adrenal cortex. It can be expected that in animals, living under unfavorable conditions, basal concentration of glucocorticoid hormones would be increased while adrenocortical response to acute stress would be weakened. Since the main function of stress-reaction is resources mobilization meant to compensate an environmental impact, its weakening should lead to reduction of reserve metabolic capacities. To test this hypothesis, we compared energy metabolism, body temperature, and corticosterone concentration in blood plasma measured in northern red-back voles (Myodes rutilus) before and after acute cooling in helium-oxygen mixture. Voles belonged to two populations that deffered in relative abundance. It is found out that voles from a population of low relative abundance inhabiting the recreational forest of Novosibirsk Scientific Center, despite their being more stress-prone and having weakened stress-reaction, have higher maximum metabolic rate than voles from the mountain taiga polulation with high relative abundance. The results obtained suggest that living under unfavorable conditions leads to physiological adaptations which enhance resistance to acute stress, yet increase the risk of chronic stresses that have negative effect on fitness.

Exposing broiler eggs to green, red and white light during incubation

Previous work has shown that exposing broiler eggs to white light during incubation can improve hatchability and post-hatch animal welfare. It was hypothesized that due to how different wavelengths of light can affect avian physiology differently, and how pigmented eggshells filter light that different monochromatic wavelengths would have differential effects on hatchability and post-hatch animal welfare indicators. To determine, we incubated chicken eggs (n=6912) under either no light (dark), green light, red light or white light; the light level was 250 lux. White and red light were observed to increase hatch of fertile (P<0.05) over dark and green light incubated eggs. White, red and green light exposure during incubation improved (P<0.05) the proportion of non-defect chicks over dark incubated eggs. Post-hatch 45-day weight and feed conversion was not affected by light exposure of any wavelength (P>0.05). Fear response of during isolation and tonic immobility was reduced (P<0.05) in broilers incubated under white or red light when compared with either green or dark broilers. Broilers incubated with white or red light had lower (P<0.05) composite asymmetry scores and higher (P<0.05) humoral immunity titers than dark incubated broilers, however, green light broilers did not differ (P>0.05) from dark incubated broilers. All light incubated broilers had lower (P<0.05) plasma corticosterone and higher (P<0.05) plasma serotonin concentrations than dark incubated broilers. These results indicate that white light and red light that is a component of it are possibly the key spectrum to improving hatchability and lower fear and stress susceptibility, whereas green light is not as effective. Incubating broiler eggs under these spectrums could be used to improve hatchery efficiency and post-hatch animal welfare at the same time.

Geographic variation and within-individual correlations of physiological stress markers in a widespread reptile, the common garter snake (Thamnophis sirtalis)

Characterizing the baseline and stress-induced hormonal, metabolite, and immune profiles of wild animals is important to assess the impacts of variable environments, including human-induced landscape changes, on organismal health. Additionally, the extent to which these profiles are coordinated across physiological systems within individuals remains an important question in understanding how stressors can differentially affect aspects of an individual's physiology. Here, we present data from wild populations of the common garter snake (Thamnophis sirtalis) on both baseline and stress-induced biomarkers: plasma corticosterone (CORT) concentration, plasma glucose concentration, and whole blood heterophil:lymphocyte ratio. Using a standardized restraint protocol with individuals from populations in disparate portions of this species' range – the Sierra Nevada Mountains of California and the plains of Iowa – we collected blood plasma samples at nine time points over three days. Both CORT and glucose response curves differed between georegions, with Iowa snakes attaining higher glucose concentration and maintaining elevated CORT and glucose levels for a longer duration. Additionally, both the total amount and proportional increases of CORT and glucose were lower in larger and therefore older snakes, suggesting ontogenetic shifts in stress perception or response. Within-individual correlation among the three physiological indicators was significant at the time of capture, absent after 3h in captivity, and partially restored after 3days in captivity, demonstrating the effect of stress on the relationships among these physiological systems. Together, these results provide further evidence for the great physiological flexibility of ectothermic tetrapods in maintaining homeostasis across a range of factors.

Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment

The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail.In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range.Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion.In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN.

Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress

Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d–4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60–65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FLX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (≈40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FLX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FLX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FLX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of ≈2.5% after 24h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naïve rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FLX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output may be due to reduced melanocortin signaling. Therefore, complex interactions between hypothalamic CRH and POMC might be determining the adaptive nature of the response of adult male rats to FLX and/or stress.

Intracellular signalling and plasma hormone profiles associated with the expression of unconditioned and conditioned fear and anxiety in female rats

There is considerable overlap in the neural regions and intracellular signalling pathways implicated in anxiety and fear, although less is known in females. Here, we investigated whether unconditioned and conditioned fear are associated with distinct patterns of expression of extracellular signal-regulated kinase-1 and -2 (ERK1/2), protein kinase B (Akt), and calcineurin (CaN) (proteins that are key regulators of the expression of and/or memory processes of fear and anxiety) in the dorsal and ventral hippocampus, medial prefrontal cortex, and amygdala (important regions in neural fear circuitry) of adult female rats, and used a multivariate approach to find patterns of signalling that might discriminate between the different states of fear. To isolate fear to the conditioned cue from generalized fear to the test context, rats were conditioned to an auditory tone (i.e. tone paired with footshock) and twenty-four hours later exposed to a novel context in the presence or absence of the conditioned cue. A third group that was exposed to the conditioning context without undergoing fear conditioning was included to control for unconditioned responses to the testing procedures, which are anxiogenic. A discriminate function analysis and MANOVA determined that hippocampal signalling best discriminated the three groups from each other. The addition of values for plasma concentrations of corticosterone and progesterone (as indices of activation of the hypothalamic-pituitary-adrenal stress axis) to statistical analyses increased the separation of the three groups. There was high degree of association among the three signalling molecules in the four brain regions within each group. There was an absence of the associations between the medial prefrontal cortex and the amygdala in the cued fear recall group that were strong for the non-conditioned group. These results demonstrated unique neuronal and hormonal signalling profiles associated with unconditioned, generalized, and conditioned fear expression in females and highlight the importance of including appropriate comparisons to best discriminate between these different emotional states.

Central administration of neuropeptide Y differentially regulates monoamines and corticosterone in heat-exposed fed and fasted chicks

Recently, we demonstrated that brain neuropeptide Y (NPY) mRNA expression was increased in heat exposed chicks. However, the functions of brain NPY during heat stress are unknown. This study was conducted to investigate whether centrally administered NPY affects food intake, rectal temperature, monoamines, stress hormones and plasma metabolites in chicks under high ambient temperatures (HT). Five or six-day-old chicks were centrally injected with 0, 188 or 375pmol of NPY and exposed to either HT (35±1°C) or a control thermoneutral temperature (CT; 30±1°C) for 3h whilst fed or fasted. NPY increased food intake under both CT and HT. NPY reduced rectal temperature 1 and 2h after central administration under CT, but not under HT. Interestingly, NPY decreased brain serotonin and norepinephrine concentrations in fed chicks, but increased concentrations of brain dopamine and its metabolites in fasted and fed chicks, respectively. Plasma epinephrine was decreased by NPY in fed chicks, but plasma concentrations of norepinephrine and epinephrine were increased significantly by NPY in fasted-heat exposed chicks. Furthermore, NPY significantly reduced plasma corticosterone concentrations in fasted chicks. Plasma glucose and triacylglycerol were increased by NPY in fed chicks, but triacylglycerol declined in fasted NPY-injected chicks. In conclusion, brain NPY may attenuate the reduction of food intake during heat stress and the increased brain NPY might be a potential regulator of the monoamines and corticosterone to modulate stress response in heat-exposed chicks.

Individual and interactive sex-specific effects of acute restraint and systemic IFN-γ treatment on neurochemistry

Compelling evidence supports the involvement of the pro-inflammatory cytokines, IL-6, IFN-α and TNF-α in depression and related stress-associated pathologies. A role has also been suggested for the Th1-type cytokine, IFN-γ, with most mechanistic accounts focusing on the cytokine's capacity to induce indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is surprisingly little evidence directly linking IFN-γ to alterations of brain regional monoamine activity and HPA axis functioning. Our specific aims in the present study were twofold: 1) assess the behavioural, plasma corticosterone and brain regional monoamine effects of acute systemic IFN-γ, with or without short duration restraint stress (15 min), and 2) determine the sex-specific nature of these effects. As predicted, IFN-γ stimulated monoaminergic activity within a number of stressor-sensitive limbic brain regions, most notably the paraventricular nucleus of the hypothalamus, central amygdala and prefrontal cortex. While several of these effects were sex-specific, there was little in the way of synergism between the cytokine and stressor treatments. Nonetheless, IFN-γ did synergistically interact with acute restraint stress to increase plasma corticosterone concentrations, and this effect was most pronounced in the male mice. These data are among the first to show that systemically administered IFN-γ can alone or in conjunction with psychologically relevant stressor, modify brain regional monoamine activity and the plasma corticosterone response.