Hypothalamo Pituitary Research Articles

Effect of human presence and handling on circulating corticosterone levels in breeding blue tits ( Parus caeruleus)

Birds may react to the presence of humans with an immediate primary behavioural reaction and with physiological responses, such as the activation of the hypothalamo–pituitary–adrenal axis. This study investigates the suite of behavioural and adrenocortical responses to the presence of humans and to handling in two subspecies of blue tits Parus caeruleus, a small hole-nesting passerine, during the period of feeding their nestlings. The first aim was to investigate whether the presence of humans near their nests elicits an adrenocortical response and whether the increase in circulating corticosterone is correlated with the behavioural reaction of the birds. The second aim was to determine the time-lag between the onset of capture and handling stress and the increase in circulating corticosterone levels. The third aim was to try to explain individual variation in the adrenocortical response to handling with 9 intrinsic and extrinsic factors (sex, age, body size, measures of body condition, time of day, and date). One half of the parents showed a behavioural reaction to our presence near the nest, such as alarming, and hesitating to enter the nestbox. However, the degree of behavioural reaction before handling was not related to circulating corticosterone levels which remained low. The results confirm that primary behavioural and adrenocortical reactions to the presence of predators are independent of each other. A comparison with published findings supports the hypothesis that birds react to predators with an adrenocortical response only in a situation that is imminently life-threatening. Hence, the primary behavioural response of the bird to a predator may determine whether or not an adrenocortical response is elicited. An adrenocortical response to handling started 3 min after capture in the nest box. Individual variation in baseline corticosterone levels could be explained by subspecies and body condition (fat stores), variation in handling-induced corticosterone levels by subspecies, body condition, body size, and time of day.

Testosterone induces testicular development but reduces GnRH-I fiber density in the brain of the House Finch, Carpodacus mexicanus

Testosterone (T) in male birds generally inhibits the activity of the hypothalamo–pituitary–gonadal axis, but the androgen can also be gonadostimulatory. The mechanisms responsible for this stimulation are unknown. To address this question, adult male House Finches, Carpodacus mexicanus, held on short day length to inhibit reproductive function, received 20-mm long T-filled Silastic capsules either for 74 days (T+; n = 5; Day 1–74) or for 66 days followed by eight days without capsules (T−; n = 5), or empty capsules for 74 days (controls, C, n = 10). At sacrifice on Day 74, plasma T concentrations were elevated in T+ males and low, and similar in T− and C males. Testes were enlarged in T+ males (136.5 ± 57.2 mg), small in T− males (16.2 ± 9.5 mg), and undeveloped in C males (5.4 ± 3.6 mg). The three groups had similar numbers and sizes of hypothalamic gonadotropin-releasing hormone-I immunoreactive (GnRH-I ir) perikarya, but perikaryon GnRH-I ir labelling was lighter in T+ than C males. T+ males also had lower density of GnRH-immunolabelled fibers in the preoptic area and lower intensity of GnRH immunolabelling in the median eminence than C males, suggesting an inhibition of GnRH-I neuronal activity. Plasma luteinizing hormone in the three experimental groups was uniformly low and did not differ. Thus, T administration-induced testicular development was associated with an inhibition of the reproductive neuroendocrine system, demonstrating a direct stimulatory effect of T on testes. Stimulation of testicular function by endogenous T in seasonal breeders may contribute to the rapid gonadal maturation that takes place in response to photostimulation.

Comparison of the effects of proton pump inhibitors on human plasma adrenocorticotropic hormone and cortisol levels under the starved condition

The hypothalamo–pituitary–adrenal (HPA) axis is known to relate with energy homeostasis. Appetite and food intake are assumed to be regulated by the HPA axis. Among lots of medicines that act gastrointestinal system, we focused proton pump inhibitors, which are widely used to treat peptic ulcer, gastro esophageal reflux disease and eradication of Helicobacter pylori. In this study, we investigated that the effect of three proton pump inhibitors (omeprazole, lansoprazole and rabeprazole) on plasma adrenocorticotropic hormone (ACTH) and cortisol levels in healthy human subjects. Five healthy male volunteers were treated to omeprazole, lansoprazole, rabeprazole or placebo. Venous blood samples were taken repetitively from a forearm vein before and after administration. Plasma ACTH-like immunoreactive substance (IS) levels were measured using a sensitive enzyme immunoassay, and plasma cortisol levels were measured using a fluorescence polarization immunoassay. Single administration of lansoprazole caused significant ( P < 0.05) increase of ACTH-IS at 60 and 120–180 min, and cortisol at 180–240 min after administration, compared with placebo group. Rabeprazole also caused significant increase of ACTH-IS at 120 min and cortisol at 240–360 min, compared with placebo group. Omeprazole had no effect on plasma ACTH-IS and cortisol levels. Lansoprazole and rabeprazole increased plasma ACTH-IS and cortisol levels. Therefore, we hypothesized that the medicines might activate the HPA axis, and have effect to promote feeding. We considered that these results might be relevant to the development of new therapeutics in the treatment of psychiatric disorders involving dysregulation of appetite.

Analgesia and hyperalgesia from CRF receptor modulation in the central nervous system of Fischer and Lewis rats

This study examines the contribution of central corticotropin-releasing factor (CRF) to pain behavior. CRF is the principal modulator of the hypothalamo–pituitary–adrenal (HPA) axis, in addition to acting on many other areas of the central nervous system. We compared nociceptive thresholds (heat and mechanical) and pain behavior in response to a sustained stimulus (formalin test) between Fischer and Lewis rats that have different HPA axis activity. Intracerebroventricular (i.c.v.) administration of CRF produced dose-dependent antinociception at a lower dose in Lewis (40 ng, paw pinch 71 ± 0 g) compared to Fischer rats (200 ng, 112 ± 3 g). The antinociceptive effect of CRF was mostly preserved in adrenalectomized Fischer rats. The i.c.v. administration of the CRF receptor antagonist, astressin, had a hyperalgesic effect, suggesting that CRF is tonically active. Lewis rats required higher doses of astressin (5 ng, paw pinch 51 ± 1 g) to show nociceptive effects compared to Fischer rats (1 ng, 79 ± 1 g). Only Lewis rats vocalized during mechanical stimulus, and this behavior was prevented by diazepam or morphine but was worsened by CRF, despite its antinociceptive property. In the formalin test, CRF and astressin had the largest effect on the interphase suggesting that they act on the endogenous pain inhibitory system. CRF also increased anxiety/fear-like behaviors in the forced swim and predator odor tests. Our results establish that central CRF is a key modulator of pain behavior and indicates that CRF effects on nociception are largely independent of its mood modulating effect as well as its control of the HPA axis.

ACTH cells of pituitary pars distalis of viscacha ( Lagostomus maximus maximus): Immunohistochemical study in relation to season, sex, and growth

Corticotrope or ACTH cells were immunohistochemically identified in the pituitary pars distalis (PD) of viscacha by using the polyclonal antiserum against ACTH (1–24). The localization, distribution, shape, percentage immunopositive area, and major cellular and nuclear diameters of these cells were analyzed by image analysis in adult male viscachas captured in their natural habitat during the year and after the chronic administration of melatonin. The same parameters were analyzed in immature male and adult female viscachas. ACTH cells in adult males were mainly localized in the dorsal and cephalic regions of PD. They were isolated, forming small groups and in contact with follicular structures and blood vessels. They were pleomorphic, with some of them being polygonal, oval, round, and others, stellate with cytoplasmic extensions. The percentage immunopositive area and the major cellular diameter showed seasonal variations with lower values during June and July (early winter). A decrease in the percentage immunopositive area was observed after the administration of melatonin in adult male animals. ACTH cells of immature animals differed from the adults’ cells in their distribution, shape, pattern of immunolabeling, and percentage immunopositive area. These parameters in adult females did not vary in relation to adult males at the same time of the year although. However, the cells in females were smaller in size during April–May. In pregnant viscachas (June–July), these parameters did not show significant differences with the results of non-pregnant females (April–May). This suggests that the environmental stressors do not exert the same influence on the hypothalamo–pituitary–adrenal axis in adult male and female viscachas, probably due to the physiological changes caused by pregnancy. Our results in adult male viscacha demonstrate that the morphology of the ACTH cells varies according to the different seasonal conditions, thus participating in the adaptation process of this rodent to the environment. The elevated levels of melatonin during winter months might inhibit the synthesis of ACTH, probably when affecting some secretagogue of this pituitary hormone. Moreover, the morphological variations observed between adult and immature male viscachas and between both sexes suggest that the steroid gonadal hormones might act on the development and activity of ACTH cells.

The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-Diol Inhibit the Hypothalamo–Pituitary–Adrenal Response to Stress by Acting through Estrogen Receptor β-Expressing Neurons in the Hypothalamus

Estrogen receptor beta (ERbeta) and androgen receptor (AR) are found in high levels within populations of neurons in the hypothalamus. To determine whether AR or ERbeta plays a role in regulating hypothalamo-pituitary-adrenal (HPA) axis function by direct action on these neurons, we examined the effects of central implants of 17beta-estradiol (E2), 5alpha-dihydrotestosterone (DHT), the DHT metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol), and several ER subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH) response to immobilization stress. In addition, activation of neurons in the paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression. Pellets containing these compounds were stereotaxically implanted near the PVN of gonadectomized male rats. Seven days later, animals were killed directly from their home cage (nonstressed) or were restrained for 30 min (stressed) before they were killed. Compared with controls, E2 and the ERalpha-selective agonists moxestrol and propyl-pyrazole-triol significantly increased the stress induced release of corticosterone and ACTH. In contrast, central administration of DHT, 3beta-diol, and the ERbeta-selective compound diarylpropionitrile significantly decreased the corticosterone and ACTH response to immobilization. Cotreatment with the ER antagonist tamoxifen completely blocked the effects of 3beta-diol and partially blocked the effect of DHT, whereas the AR antagonist flutamide had no effect. Moreover, DHT, 3beta-diol, and diarylpropionitrile treatment significantly decreased restraint-induced c-fos mRNA expression in the PVN. Together, these studies indicate that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3beta-diol and subsequent binding to ERbeta.

The counterbalance between leptin and cortisol may be associated with comorbid depression and anxiety

Details of the psychopathologic relationship that exists between major depression and leptin are uncertain. However, the comorbidity which is known to occur between major depression and anxiety disorders may help elucidate this controversy. In addition to their comments on the heterogeneity of obsessive-compulsive disorder (OCD), Atmaca and colleagues have also provided important insight regarding the heterogeneity of major depression. 1 In theory, hyperactivity of the hypothalamo–pituitary–adrenal (HPA) axis, yielding an elevated level of cortisol, is an important pathogenic factor for major depression. From a dynamic perspective, previous neuroendocrinological studies have established that the HPA axis responds quickly to acute stress. The HPA axis also has the capacity to adapt to chronic stress so that further responsiveness is maintained. 2 Leptin, a neuropeptide derived primarily from peripheral adipose tissue, may provide negative feedback inhibition to the HPA axis which is crucial for adapting to chronic stress. 2 Psychopathology would be the result if such a mechanism of counterbalance was impaired. Hence, compromised suppression of cortisol secretion by a reduced level of leptin could precipitate major depression. It is thus feasible that the role of leptin to a hyperfunctioning HPA axis, as occurs in major depression, may be influenced by a psychiatric comorbidity. Many community-based epidemiological studies have shown that major depression is often accompanied by anxiety disorders. Hypoleptinemic subjects with both major depression and OCD may in fact have an impaired feedback loop involving the HPA axis, which in turn may contribute to hyperactivity of the HPA axis. In a study involving the victims of a giant earthquake, hyperleptinemia was demonstrated in the subjects exhibiting persistent partial posttraumatic stress disorder (PTSD), yet during an 18-month followup did not meet the diagnostic criteria of major depression. 3 Hypothetically, hyperleptinemia may correlate with excessive inhibition of the HPA axis, manifesting as a lower cortisol level in PTSD. The activity of the HPA axis differs between PTSD and major depression. 4 However, dysfunction of the counterbalance between leptin and cortisol in the opposing direction, irrespective of the cause (i.e. PTSD or major depression with comorbid OCD), is plausible. Future research which investigates the relationship between major depression and leptin should consider psychiatric comorbidities. Such a possibility has not been addressed by previous studies. Structured diagnostic algorithms may be required to identify an anxiety syndrome. Those with pure major depressive episodes and with comorbid anxiety disorders may have a different etiology in the pattern or impact of the leptin–cortisol interaction.

Modulation of the hypothalamo–pituitary–adrenocortical axis by caffeine

Although caffeine is the most consumed psychoactive substance in the world, the extents of many of its effects are unknown. High doses of caffeine have been shown to activate the HPA axis while the effects of low to moderate doses have usually not been described in detail. Moreover, although several lines of evidence suggest that low doses of caffeine may restrain some negative affective states, the possible modulatory role of caffeine on HPA axis activation induced by a stressful stimulus has not been described. Thus, the present studies investigated the possible modulatory effects of low to moderate doses of caffeine on moderate to high HPA axis activation induced by different intensities of loud noise. First, in order to test this modulation, time courses for adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone levels peaked 30 min from the onset of noise presentation, and rapidly declined after noise termination. A low caffeine dose of 2 mg/kg significantly increased plasma corticosterone and ACTH levels 30 min following injections, but levels returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and higher elevated plasma hormone levels for at least 2h. Doses of 2 or 10mg/kg, however, did not modulate endocrine responses to loud noise presentation. It is concluded that although caffeine activates the HPA axis, low to moderate doses do not modulate HPA axis responses to stressful stimuli.

Effects of chronic renal failure on hypothalamo–pituitary –testicular axis function and fertility in rats and humans

Effects of chronic renal failure on hypothalamo–pituitary –testicular axis function and fertility in rats and humans

Corticotrophin-releasing factor type 2 receptor-mediated suppression of gonadotrophin-releasing hormone mRNA expression in GT1-7 cells

Corticotrophin-releasing factor (CRF) released during stress has been implicated in the suppression of the hypothalamo–pituitary–gonadal (HPG) axis, especially the gonadotrophin-releasing hormone (GnRH) pulse generator, the central neural regulator of pituitary LH and FSH secretion, resulting in reproductive dysfunction. The gonadal steroid 17β-oestradiol (E2) has been shown to enhance CRF- and stress-induced suppression of pulsatile LH secretion. In the present study, we investigated the potential direct action of CRF on GnRH neurones by using GT1-7 cells, an established GnRH cell line. Furthermore, we investigated the modulatory influence of E2 on the effects of CRF and expression of CRF type 2 receptors (CRF-R2). Expression of CRF-R2 in the GT1-7 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). CRF produced a dose-dependent suppression of GnRH mRNA expression, an effect reversed by the selective CRF-R2 antagonist, astressin2-B (Ast2-B). E2 combined with CRF resulted in a greater suppression of GnRH expression compared with either treatment alone. E2 also increased CRF-R2 expression. These results demonstrate for the first time expression of CRF-R2 in the GT1-7 cells and suggest that CRF may directly regulate GnRH gene expression, an effect mediated, at least in part, by CRF-R2. They also raise the possibility that up-regulation of CRF-R2 may contribute to the sensitising influence of E2 on CRF- and stress-induced suppression of the GnRH pulse generator.

Behavioral, central monoaminergic and hypothalamo–pituitary–adrenal axis correlates of fear-conditioned analgesia in rats

Fear-conditioned analgesia is an important survival response which is expressed upon re-exposure to a context previously paired with a noxious stimulus. The aim of the present study was to characterize further the behavioral, monoaminergic and hypothalamo–pituitary–adrenal axis alterations associated with expression of fear-conditioned analgesia. Rats which had received footshock conditioning 24 h earlier, exhibited reduced formalin-evoked nociceptive behavior upon re-exposure to the footshock chamber, compared with non-footshocked formalin-treated rats. Intra-plantar injection of formalin reduced the duration of contextually-induced freezing and 20–40 kHz ultrasound emission. Intra-plantar injection of formalin to non-footshocked, non-conditioned rats did not induce ultrasonic vocalizations. Intra-plantar injection of formalin to footshock-conditioned rats, significantly increased tissue levels of 3,4-dihydroxyphenylacetic acid and the 3,4-dihydroxyphenylacetic acid:dopamine ratio in the periaqueductal gray and reduced levels of dopamine in the thalamus, compared with saline-treated footshocked controls. Non-footshocked, non-conditioned rats were capable of mounting a robust formalin-evoked increase in plasma corticosterone levels. Moreover, plasma corticosterone levels were significantly higher in saline-treated, footshock conditioned rats compared with saline-treated non-footshocked rats and levels did not differ between saline- and formalin-treated footshock conditioned rats. Assessment of the effects of the intra-plantar injection procedure revealed an attenuation of short-term extinction of contextually-induced freezing in rats anesthetized for intra-plantar injection of saline compared with non-anesthetized, non-injected rats as well as discrete effects on monoamines, their metabolites and plasma corticosterone levels. These data extend behavioral characterization of the phenomenon of fear-conditioned analgesia and suggest that measurement of ultrasound emission may be used as an ethologically relevant index of the defense response during fear-conditioned analgesia. Ultrasonic vocalization may also be a useful behavioral output to aid separation of nociception and aversion. The data provide evidence for discrete alterations in dopaminergic activity in the periaqueductal gray and thalamus and for altered hypothalamo–pituitary–adrenal axis activity following expression of defensive behavior.

Perinatal maternal undernutrition programs the offspring hypothalamo–pituitary–adrenal (HPA) axis

There is now compelling evidence, coming both from animal and human studies that an early exposure to undernutrition is frequently associated with low birth weight and programs HPA axis alterations throughout the lifespan. Although animal models have reported conflicting findings arising from differences in experimental paradigms and species, they have clearly demonstrated that such programming not only affects the brain but also the pituitary corticotrophs and the adrenal cortex. In fetuses, maternal undernutrition reduces HPA axis function and implicates a reduction of placental 11β-HSD2 activity and a greater transplacental transfer of glucocorticoids (GRs). In young adults, usually only fine HPA axis alterations were observed, whereas in older ones, maternal undernutrition was frequently associated with chronic hyperactivity of this neuroendocrine axis. In humans, evidence of HPA axis dysregulation in people who were small at birth has recently emerged. Thus, we suggest that such alterations in adults may be implicated in the aetiology of several disorders related to the metabolic syndrome as well as to immune or inflammatory diseases. To reverse such programming, recent experimental reports have shown that postnatal environmental interventions, dietary modifications and the use of agents modulating the epigenomic state could partly restore physiological functions and thus open new therapeutic strategies.

A paracrine component of salient symptoms of depression in Cushing’s of diencephalic origin, and in perimenstrual syndromes: A hypothesis

Interrelationships between adrenocortical secretions and depression syndromes have been known since early in the 20th century. Now, the fact that pregnane and pregnene steroids are also known to be synthesized in the brain (they are termed neurosteroids (NS)), raises the possibility that these natural compounds could have paracrine effects. Adrenocorticotropic hormone (ACTH) can modulate biosynthesis of NSs. 17beta estradiol has been shown to decrease THP concentration in the brain. It is hypothesized that imbalance between stimulatory and depressant NSs induced by ACTH elevation in hypothalamo pituitary dependent Cushing's, and by estrogen concentration changes during the menstrual cycle, may be associated with the pathophysiology of salient symptoms of depression in Cushing's and in perimenstrual syndromes.

Relationships among the behavioral, noradrenergic, and pituitary–adrenal responses to interleukin-1 and the effects of indomethacin

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo–pituitary–adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1β (1 μg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2–4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1β injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1β also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1β-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1β-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.

Healing by gentle touch in musculoskeletal disorders

The Centre for Complementary Care, Muncaster (The Centre), provides healing by gentle touch: a non-invasive intervention that is complementary to conventional medicine and involves the gentle placing of hands on various parts of the body. An outcomes study at The Centre has recorded clients’ perceptions of their health status, both before and after treatment, using validated research tools. A subgroup of clients attending The Centre with largely long-term, intractable musculoskeletal disorders (including osteoarthritis and various joint/back injuries) reported significant reductions in stress and pain, increased ability to cope and to carry out usual activities, improved relaxation levels, reduced medication use and decreased disability after four healing sessions. Those participants with the most severe symptoms on entry showed the most substantial improvement. Some of the processes that might be responsible for the improvements in these subjects include the modification of stress and pain pathways by particular psychological and physiological aspects of healing. The psychological mediators include love, caring, willingness to treat and aspects of the therapeutic relationship. The physiological mediators include touch, warmth and relaxation. These interact indirectly with the hypothalamo–pituitary–adrenal (HPA) axis and related systems to ease those aspects of the ailment that are exacerbated by stress, thus greatly reducing symptoms and facilitating endogenous healing mechanisms. The intensity and significance of pain may be lowered by modification of both the interpretation of the sensory input, and the psychological component of the pain experience. This is likely to result in a change in the perception of pain severity, the quality of the pain and the level of distress it produces. These findings suggest that healing may be a valuable adjuvant to other therapeutic interventions.

Neuroactive steroids attenuate oxytocin stress responses in late pregnancy

In late pregnant rats neuroendocrine stress responses, expressed as increased oxytocin secretion and activation of the hypothalamo–pituitary–adrenal axis, are attenuated. These adaptations preserve the oxytocin store for parturition and prevent pre-term birth, and protect the fetuses from adverse programming by exposure to excess glucocorticoid. Mechanisms of adaptations for oxytocin neurones are reviewed, using challenge with systemic interleukin-1β, simulating activation of immune signaling by infection, as a stressor of special relevance in pregnancy. In virgin rats, systemic interleukin-1β stimulates the firing of oxytocin neurones, and hence oxytocin secretion, but interleukin-1β has no effects in late pregnant rats. This lack of response is reversed by naloxone treatment just before interleukin-1β administration, indicating endogenous opioid suppression of oxytocin responses in late pregnancy. This opioid presynaptically inhibits noradrenergic terminals impinging on oxytocin neurones. Finasteride pretreatment, inhibiting progesterone conversion to allopregnanolone, a positive GABA A receptor allosteric modifier, also restores an oxytocin response to interleukin-1β. This finasteride effect is reversed by allopregnanolone treatment. In virgin rats allopregnanolone attenuates the oxytocin response to interleukin-1β, which is exaggerated by naloxone. The effects of naloxone and finasteride in late pregnant rats in restoring an oxytocin response to interleukin-1β are not additive. Accordingly, allopregnanolone may both enhance GABA inhibition of oxytocin neurone responses to interleukin-1β, and induce opioid suppression of noradrenaline release onto oxytocin neurones.

Beneficial effects of exercise and its molecular mechanisms on depression in rats

Exercise showed the beneficial effects on mental health in depressed sufferers, whereas, its underlying mechanisms remained unresolved. This study utilized the chronic unpredictable stress (CNS) animal model of depression to evaluate the effects of exercise on depressive behaviors and spatial performance in rats. Furthermore, we tested the hypothesis that the capacity of exercise to reverse the harmful effects of CNS was relative to the hypothalamo–pituitary–adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Animal groups were exposed to CNS for 4 weeks with and without access to voluntary wheel running. Stressed rats consumed significantly less of a 1% sucrose solution during CNS and exhibited a significant decrease in open field behavior. On the other hand, they showed impaired spatial performance in Morris water maze test 2 weeks after the end of CNS. Further, CNS significantly decreased hippocampal BDNF mRNA levels. However, voluntary exercise improved or even reversed these harmful behavioral effects in stressed rats. Furthermore, exercise counteracted a decrease in hippocampal BDNF mRNA caused by CNS. In addition, we also found that CMS alone increased circulating corticosterone (CORT) significantly and decreased hippocampal glucocorticoid receptor (GR) mRNA. At the same time, exercise alone increased CORT moderately and did not affect hippocampal GR mRNA levels. While, when both CNS and exercise were combined, exercise reduced the increase of CORT and the decrease of GR caused by CMS. The results demonstrated that: (1) exercise reversed the harmful effects of CNS on mood and spatial performance in rats and (2) the behavioral changes induced by exercise and/or CNS might be associated with hippocampal BDNF levels, and in addition, the HPA system might play different roles in the two different processes.

A detailed characterization of loud noise stress: Intensity analysis of hypothalamo–pituitary–adrenocortical axis and brain activation

The present studies were undertaken to help determine the putative neural circuits mediating activation of the hypothalamo–pituitary–adrenocortical (HPA) axis and the release of adrenocorticotropin hormone (ACTH) and corticosterone in response to the perceived threat of loud noise. This experiment involved placing rats in acoustic chambers overnight to avoid any handling and context changes prior to noise exposure, which was done for 30 min (between 9:00 and 10:00 am) at intensities of 80, 85, 90, 95, 100, 105, and 110 dBA in different groups ( n = 8), and included a background condition (60 dBA ambient noise). This manipulation produced a noise-intensity-related increase in plasma ACTH and corticosterone levels, with levels beginning to rise at approximately 85 dBA. c- fos mRNA induction was very low in the brains of the control and 80 dBA groups, but several brain regions displayed a noise-intensity-related induction. Of these, several forebrain regions displayed c- fos mRNA induction highly correlated ( r > 0.70) with that observed in the paraventricular hypothalamic nucleus and plasma ACTH levels. These regions included the ventrolateral septum, the anteroventral subiculum, several preoptic nuclei, the anterior bed nucleus of the stria terminalis (BNST), the anterior paraventricular nucleus of the thalamus, and the medial subdivision of the medial geniculate body. Together with prior findings with audiogenic stress, the present results suggest that either or both the anterior BNST or the lateral septum is ideally situated to trigger HPA axis activation by stimuli that are potentially threatening.

Responses of calves to acute stress: Individual consistency and relations between behavioral and physiological measures

The present study examined the consistency over time of individual differences in behavioral and physiological responsiveness of calves to intuitively alarming test situations as well as the relationships between behavioral and physiological measures. Twenty Holstein Friesian heifer calves were individually subjected to the same series of two behavioral and two hypothalamo–pituitary–adrenocortical (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open field, OF) and novel object (NO) tests involved measurement of behavioral, plasma cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles were determined after administration of exogenous CRH and ACTH, respectively, in the HPA axis reactivity tests. Principal component analysis (PCA) was used to condense correlated measures within ages into principal components reflecting independent dimensions underlying the calves' reactivity. Cortisol responses to the OF and NO tests were positively associated with the latency to contact and negatively related to the time spent in contact with the NO. Individual differences in scores of a principal component summarizing this pattern of inter-correlations, as well as differences in separate measures of adrenocortical and behavioral reactivity in the OF and NO tests proved highly consistent over time. The cardiac response to confinement in a start box prior to the OF test was positively associated with the cortisol responses to the OF and NO tests at 26 weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical and behavioral responses to novelty. These findings strongly suggest that the responsiveness of calves was mediated by stable individual characteristics. Correlated adrenocortical and behavioral responses to novelty may reflect underlying fearfulness, defining the individual's susceptibility to the elicitation of fear. Other independent characteristics mediating reactivity may include activity or coping style (related to locomotion) and underlying sociality (associated with vocalization).

Short periods of prenatal stress affect growth, behaviour and hypothalamo–pituitary–adrenal axis activity in male guinea pig offspring

Prenatal stress can have profound long-term influences on physiological function throughout the course of life. We hypothesized that focused periods of moderate prenatal stress at discrete time points in late gestation have differential effects on hypothalamo-pituitary-adrenal (HPA) axis function in adult guinea pig offspring, and that changes in HPA axis function will be associated with modification of anxiety-related behaviour. Pregnant guinea pigs were exposed to a strobe light for 2 h on gestational days (GD) 50, 51, 52 (PS50) or 60, 61, 62 (PS60) (gestation length approximately 70 days). A control group was left undisturbed throughout pregnancy. Behaviour was assessed in male offspring on postnatal day (PND)25 and PND70 by measurement of ambulatory activity and thigmotaxis (wall-seeking behaviour) in a novel open field environment. Subsequent to behavioural testing, male offspring were cannulated (PND75) to evaluate basal and activated HPA axis function. Body weight was significantly decreased in adult PS50 and PS60 offspring and this effect was apparent soon after weaning. The brain-to-body-weight ratio was significantly increased in adult PS50 males. Basal plasma cortisol levels were elevated in PS50 male offspring throughout the 24 h sampling period compared with controls. In response to an ACTH challenge and to exposure to an acute stressor, PS60 male offspring exhibited elevated plasma cortisol responses. Plasma testosterone concentrations were strikingly decreased in PS50 offspring. Thigmotaxis in the novel environment was increased in PS50 male offspring at PND25 and PND70, suggesting increased anxiety in these animals. In conclusion, prenatal stress during critical windows of neuroendocrine development programs growth, HPA axis function, and stress-related behaviour in adult male guinea pig offspring. Further, the nature of the effect is dependant on the timing of the maternal stress during pregnancy.