Showing papers in "Stress in 2004"

The awakening cortisol response: Methodological issues and significance

Abstract: The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol/l, range 4-15 nmol/l, estimated to be equivalent to about three secretory episodes). However there are no agreed norms for the absolute concentrations of free cortisol in saliva either immediately post-awakening (range of 4.7-18.5 nmol/l) or 30 min post-awakening (range of 8.6-21.9 nmol/l). This review explores reasons for these discrepancies in normative data including confounding factors such as gender, age, awakening time, light and participant adherence. Although the physiological role of the ACR has not been clearly defined evidence is discussed that suggests it is under a distinct regulatory influence, different from the rest of the diurnal cortisol secretory cycle. Despite the difficulties associated with its measurement a range of studies have demonstrated an association between the ACR and psychosocial variables, stress and health. However it remains unclear whether positive affect and good health are consistently associated with larger or smaller awakening responses. It is early days in the search for the role and significance of the ACR. Its putative role in the regulation of physiological function across the day (e.g. the immune system) and its sensitivity to psychosocial variables make it a prime candidate as an intermediary linking mind and health.

Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus

Abstract: It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

Abstract: The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Glucocorticoid Receptor Function In Vitro in Patients with Major Depression

Abstract: Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypothalamic--pituitary--adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. Interestingly, a number of studies have also demonstrated that GR function is reduced in vitro, in peripheral tissues of depressed patients, as shown by a decreased sensitivity to the effects of glucocorticoids on immune and metabolic functions. This paper reviews the in vitro studies that have examined GR function in patients with major depression, and the possible molecular mechanisms involved in GR resistance. Since several studies have demonstrated similar regulation of GR in the brain and in peripheral tissues in humans, and given limited access to brain GR in clinical populations, this review claims that in vitro studies are of particular relevance to understand the molecular mechanisms underlying GR abnormalities in patients with major depression and its regulation by antidepressant treatment.

Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress adaptation.

Abstract: Vasopressin (VP) stimulates pituitary ACTH secretion through interaction with receptors of the V1b subtype (V1bR, V3R), located in the plasma membrane of the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotropin releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting an important role for VP during adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress. Vasopressinergic regulation of ACTH secretion depends on the number of V1bRs as well as coupling of the receptor to phospholipase C (PLC) in the pituitary. Regulation of V1bR gene transcription may involve a number of regulatory elements in the promoter region, of which a GAGA box was shown to be essential. Although V1bR gene transcription is necessary to maintain V1bR mRNA levels, the lack of correlation between VP binding and V1bR mRNA suggests that regulation of mRNA translation is a major regulatory step of the number of V1bRs. V1bR translation appears to be under tonic inhibition by upstream minicistrons and positive regulation through protein kinase C (PKC) activation of an internal ribosome entry site (IRES) in the 5' untranslated region (5'UTR) of the mRNA. The data provide mechanisms by which regulation of hypothalamic VP and pituitary V1bR content contribute to controlling HPA axis activity during chronic stress.

Oxidative stress in university students during examinations.

Abstract: Mental stress in psychiatric disease and in daily life contributes to oxidative stress in the body. In this study we investigated a connection between possible psychological stress caused by university undergraduate examinations and oxidative stress experienced by our test subjects. Some parameters of oxidative stress (single strand breaks of DNA in lymphocytes, sensitivity to lipid oxidation and antioxidant status) were studied in medical students on the day of the examination (stress condition) and compared with the same parameters obtained from the same students during the term between two examination periods (non-stress condition). The results show that in the stress condition oxidative damage to DNA and sensitivity to lipid oxidation were significantly increased (p<0.05) when compared with the same parameters in "non-stress" conditions. A significant decrease in plasma antioxidant activity (p<0.05) in students that were under stress was observed. These results suggest that during university examinations students are under increased oxidative stress.

Acute Stress Impairs Recognition for Positive Words—Association with Stress-induced Cortisol Secretion

Abstract: Some studies suggest that stress-induced effects of cortisol on memory are modulated by the valence of the stimuli to be learned and retrieved. The present study investigated the effect of acute stress-induced cortisol secretion on acquisition and retrieval of pleasant, unpleasant and neutral words. Sixty healthy men were randomly assigned to one of the three experimental groups. Participants were either exposed to a standardized laboratory stressor (the Trier Social Stress Test) before learning a wordlist, or before retrieval, or were not stressed. Free recall and recognition were tested 24 h later. Free recall was not affected by stress exposure. For recognition, there was no main effect of the stressor, but a main effect of valence and a valence by group interaction emerged: recognition for positive words was significantly impaired when subjects were stressed before retrieval. In addition, a positive correlation between the cortisol response and errors of commission was found. The results suggest that acute stress impairs memory for positive stimuli and that stress-induced cortisol secretion interferes with accuracy of memory retrieval, i.e. the ability to discriminate true memories from false ones.

Maternal prenatal stress and 4-6 year old children's salivary cortisol concentrations pre- and post-vaccination.

Abstract: In this study influences of maternal prenatal stress on the cortisol reactions of children to a vaccination were determined. Prenatal stress at around 16 weeks of gestation was measured through questionnaires and a cortisol day curve. Cortisol reactions were determined preceding and following the vaccination. A total of 24 children (age between 3.11 and 5.9 years, mean age 4.9 years) and their mothers participated in this study. Multilevel analysis (hierarchical linear modelling) was used to analyze the data. Children of mothers who had higher concentrations of morning cortisol during pregnancy had higher concentrations of cortisol as compared to children of mothers who had lower concentrations of morning cortisol. Furthermore, more daily hassles and a higher level of fear of bearing a handicapped child during pregnancy were associated with higher concentrations of cortisol in the children.

Cortisol in Mood Disorders

Abstract: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in mood disorders Hypercortisolaemia, which has been attributed to a breakdown in glucocorticoid-receptor-mediated negative feedback mechanisms within the HPA axis, may be central to the pathogenesis of both the depressive symptoms and the cognitive deficits, which characterise severe mood disorders Strategies to normalise glucocorticoid receptor (GR) function, and thus restore HPA functional integrity, have been the focus of recent research Preliminary preclinical and clinical studies report encouraging results which suggest that lowering circulating cortisol levels, by up-regulating GRs, may have therapeutic efficacy in terms of improvements in depressive symptoms and cognitive functioning

A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor.

Abstract: Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild stressors and repeated exposures. Long-term stress-induced changes may not take place at the level of the PVN itself, but in brain nuclei showing synaptic plasticity and putatively involved in the control of the HPA axis and other physiological responses. As for the precise areas involved, these remain to be characterized.

Programming of the Hypothalamo–Pituitary–Adrenal Axis: Serotonergic Involvement

Abstract: The ability of the early environment to programme the developing hypothalamo–pituitary–adrenal (HPA) axis has been reported in several animal species. There is considerable evidence that a similar process can occur in the human, and that long-term alterations in HPA function are associated with altered susceptibility to disease in later life. The phenotype of HPA function following early manipulation depends on the timing and intensity of the manipulation as well as the gender of the fetus/neonate. There is considerable interplay between the developing HPA and the reproductive axes and emerging evidence indicates that this interaction is modified by early environmental manipulation. Studies are rapidly unravelling the mechanisms that underlie developmental programming of the HPA axis. In this context, the serotonergic system has been identified as a primary system involved in this process. Understanding the mechanisms involved in neuroendocrine programming will facilitate the development of interventions ...

Involvement and role of the hypothalamo-pituitary-adrenal (HPA) stress axis in animal models of chronic pain and inflammation.

Abstract: Hypothalamo-pituitary-adrenal (HPA) axis changes have been reported in several disease states, including major depressive disorder, rheumatoid arthritis, multiple sclerosis and various other conditions associated with chronic pain. These observations suggest that stress and the HPA axis may play important roles in the pathology of these diseases. In order to contribute to a better understanding of the role that chronic stress may play in human pathology, this review article explores the involvement of the HPA axis in those animal models of chronic pain and inflammation that entail persistent rather than intermittent stress.

Dietary Ethyl-eicosapentaenoic Acid but not Soybean Oil Reverses Central Interleukin-1-induced Changes in Behavior, Corticosterone and Immune Response in Rats

Abstract: Omega (n)-3 and n-6 fatty acids are important membrane components of neurons and immune cells, and related to psychiatric and inflammatory diseases. Increased ratio of n-6/n-3 in the blood has been...

Effects of Soy Lecithin Phosphatidic Acid and Phosphatidylserine Complex (PAS) on the Endocrine and Psychological Responses to Mental Stress

Abstract: Phosphatidylserine, derived from cow brains, has been shown previously to dampen the ACTH and cortisol response to physical stress. Further research investigated the influence of soy lecithin phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. In this study, we investigated the effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the psychological response (Spielberger State Anxiety Inventory stress subscale) to a mental and emotional stressor. Four groups of 20 subjects were treated for three weeks with daily dosages of either 400 mg PAS, 600 mg PAS, 800 mg PAS, or placebo before exposure to the Trier Social Stress Test (TSST). Treatment with 400 mg PAS resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary cortisol responses to the TSST, but did not affect heart rate. The effect was not seen with larger doses of PAS. With regard to the psychological response, 400 mg PAS seemed to exert a specific positive effect on emotional responses to the TSST. While the placebo group showed the expected increase in distress after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary-adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders.

The Influence of 17β-oestradiol on Corticotrophin-releasing Hormone Induced Suppression of Luteinising Hormone Pulses and the Role of CRH in Hypoglycaemic Stress-induced Suppression of Pulsatile LH Secretion in the Female Rat

Abstract: Corticotrophin-releasing hormone (CRH) released during stress has been implicated in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol (E2) has been shown to enhance stress-induced suppression of pulsatile gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The aims of the present study were to examine the role of CRH in hypoglycaemic stress-induced suppression of LH pulses, and to investigate the influence of E2 on the inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely prevented by intracerebroventricular (icv) administration of a CRH antagonist. Central administration of CRH (5 microg) resulted in an interruption of LH pulses in E2 treated animals, but had little or no effect in the absence of this gonadal steroid. These results provide evidence of a pivotal role for CRH in mediating the suppressive effect of IIH stress on pulsatile LH secretion in the female rat, and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.

Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion.

Abstract: Increased cortisol levels have been observed in patients suffering from a number of metabolic and psychiatric disorders. In some of these disorders a causal relationship has been suggested between the increased cortisol secretion and the observed clinical phenomena. Glucocorticoid receptor antagonists which block cortisol effects might have a benefit in both the diagnosis and treatment of these disorders. Selective glucocorticoid receptor antagonists with in vivo potency have not been described thus far, partly due to the similarity between the glucocorticoid and progesterone receptors. In the present studies, we report on three different chemical classes derived from the glucocorticoid/progestagen antagonist RU486. Selected compounds from the classes 11-monoaryl steroids, 11,21-bisaryl steroids and 11-aryl, 16-hydroxy steroids proved to be selective glucocorticoid receptor binders with in vivo antagonistic activity. Most compounds were able to pass the blood-brain barrier. These compounds offer the opportunity to investigate and possibly treat patients with a disturbed hypothalamus-pituitary-adrenal axis without side effects caused by an antiprogestagenic action.

Cytokine production by spleen cells after social defeat in mice: activation of T cells and reduced inhibition by glucocorticoids.

Abstract: Social disruption (SDR) is an effective model of social stress associated with an enhanced inflammatory reactivity of the immune system. The aim of the present study was to further describe SDR effects on cytokine production by spleen cells, testing selectively monocyte and T cell functions as a result of this stressor. For this purpose, splenocytes from control mice (C) and mice socially stressed for 7 days (SDR) were cultured in the presence of lipopolysaccharide (LPS) or concanavalin A (Con A). Splenocyte proliferation, cytokine production and sensitivity of spleen cells to corticosterone were assessed in vitro. The humoral response to keyhole limpet hemocyanin (KLH) immunization was assessed. SDR induced splenomegaly and enhanced splenocyte basal proliferation. The pro-inflammatory influence of SDR was confirmed by an increased release of interleukin-6 (IL-6) by LPS-stimulated cultures and by a reduced sensitivity of spleen cells to the anti-inflammatory effect of corticosterone. The mechanism increasing cytokine production in response to LPS was cytokine specific, since among inflammatory cytokines, IL-6 but not interferon-gamma (IFN-gamma) was enhanced by stress. In stressed mice, the increase in IL-6 and IFN-gamma and the decrease in IL-10 release in Con A-stimulated cultures indicate that SDR did not modify the Th1/Th2 cytokine balance but globally activated T cells. Plasma anti-KLH antibody levels were similar in both groups. Wounded and non-wounded mice presented similar responses to stress. This study shows that social disruption stress enhances the reactivity of cells from both the acquired and innate immune systems.

Extinction-induced neuroplasticity attenuates stress-induced cocaine seeking: a state-dependent learning hypothesis.

Abstract: Chronic drug use weakens excitatory neocortical input to the nucleus accumbens (NAc). We previously reported that extinction training, a form of inhibitory learning that progressively reduces cocaine-seeking behaviour when reward is withheld, reverses this deficit by up-regulating GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors in the NAc. The level of GluR1 up-regulation is positively associated with a reduction in cocaine seeking, suggesting that extinction-induced up-regulation in AMPA receptors in the NAc opposes motivational influences that maintain cocaine seeking. This hypothesis is supported by the finding that over-expression of GluR1 and GluR2 in the NAc facilitates extinction of cocaine self-administration. Furthermore, a single extinction training session conducted during GluR1 and GluR2 over-expression strongly and selectively attenuates the ability of an environmental stressor to trigger relapse to cocaine seeking long after ...

Cellular mechanisms underlying neuronal excitability during morphine withdrawal in physical dependence: lessons from the magnocellular oxytocin system.

Abstract: Opiates are used clinically as analgesics, but their euphoric actions can lead to continued use and to dependence and addiction. While there are many factors involved in drug abuse, avoidance of stressful withdrawal symptoms is a key feature of addiction and its treatment. Fundamental to this is the need to understand the cellular processes that induce dependence and lead to the withdrawal syndrome. Many neurones in the brain express opioid receptors but only a few types of neurone develop dependence during chronic morphine exposure. The physiology of opiate-dependent cells is altered such that they require the continued presence of the drug to function normally and this is revealed, in cells that are inhibited by initial acute exposure to opiate, by a rebound hyperexcitation upon opiate withdrawal. Hypothalamic oxytocin neurones robustly develop morphine dependence and provide an exceptional opportunity to probe the cellular mechanisms underlying morphine dependence and withdrawal excitation. Although expression of morphine withdrawal excitation by oxytocin cells requires afferent inputs, the underlying mechanisms appear to reside within the oxytocin neurones themselves and probably involve changes in the intrinsic membrane properties of these neurones.

The activity of the hypothalamo-neurohypophysial system in response to acute stressor exposure: neuroendocrine and electrophysiological observations.

Abstract: The present mini review focuses on stress-induced alterations of the electrical and secretory activity of vasopressin (AVP) and oxytocin (OXT) neurones originating within the supraoptic nucleus (SON) and constituting the hypothalamo-neurohypophysial system (HNS) in the male rat. Previously, it was thought that SON neurones are predominantly activated by osmotic and reproductive stimuli. However, recent findings also suggest a selective activation of AVP and/or OXT neurones in response to specific stressors. Inhibitory amino acids seem to participate at the level of the SON in the control of HNS activity during stress. Taurine, probably of glial origin, selectively inhibits the secretory activity of AVP neurones. In contrast, GABA, probably of neuronal origin, interferes with the release of OXT both from axon terminals into blood and from somata/dendrites into the extracellular fluid of the SON. Depending upon whether a defined stressor triggers taurine and/or GABA release within the SON the secretion of AVP and/or OXT from HNS neurones will be inhibited. These observations shed new light on the neurone-neurone and glial-neurone interactions that ensure an appropriate neuroendocrine stress response.

Measurement of Nerve Growth Factor Serum Concentration in a Psychologically Stressful Situation in Men

Abstract: Psychologically stressful events have been reported to elevate nerve growth factor (NGF) serum concentrations. NGF and cortisol serum concentrations were measured in 20 healthy male volunteers before (3 p.m.) and after (5 p.m.) an academic oral presentation and on a control day. Cortisol showed a significant overall change (p=0.001), i.e. cortisol serum concentrations were increased on the lecture day at 3 p.m. (p=0.007; 155%) and at 5 p.m. (p=0.001; 175%) as compared with the control day. In contrast to cortisol no significant differences among the four serum NGF measurements was detected (Chi-quadrat 2.94, df=3, p=0.401), i.e. the NGF serum concentrations remained unchanged on the lecture day at 3 p.m. (p=0.279) and at 5 p.m. (p=0.627) as compared with the control day. We conclude that NGF serum levels do not change during acute stress, at least after this type of stressor.

Effects of Stress on Inflammatory Autoimmune Disease: Destructive or Protective?

Abstract: We have summarised evidence in the literature for modulatory effects of stress on inflammatory autoimmune disease. We find that overall there is strong evidence for such an interrelationship. Apparent discrepancies between groups and studies are probably due to differences in experimental design, whether longitudinal or retrospective. Other important variables are the specific effects of different types of stress and the intensity and timing of the stressor relative to onset of inflammation. We conclude that there is much of benefit to be learned from scientific study of stress, such as harnessing and rationalising of stressful experiences through self-expression in patients, or the identification of novel anti-inflammatory compounds activated by stress.

Fos expression in CRF-containing neurons in the rat paraventricular nucleus after central administration of neuromedin U.

Abstract: We examined the effects of centrally administered neuromedin U (NMU) on corticotrophin-releasing factor (CRF)-containing neurons in the hypothalamic paraventricular nucleus (PVN) of rats, using double immunohistochemistry for CRF and Fos. Almost all CRF-containing neurons in the parvocellular divisions of the PVN expressed Fos-like immunoreactivity 90 min after intracerebroventricular administration of NMU (3 nmol/rat). This results suggest the possibility that central NMU may be involved in stress-induced activation of CRF-containing neurons in the PVN.

The pathology of cellular anti-stress mechanisms: a new frontier.

Abstract: Exposure to stressors is an omnipresent variable for all living organisms, which have evolved anti-stress mechanisms to deal with the consequences of stress. The chaperoning systems are among these mechanisms, and their central components are the molecular chaperones that play important roles in protein biogenesis. Recent data suggest that failure of the chaperoning systems due to defective chaperones, for example, leads to pathology. Consequently, medical researchers and practitioners must now also consider the chaperoning systems, both as potentially major players in pathogenesis and as diagnostic-prognostic indicators.

Vasopressin response to osmotic and hemodynamic stress: neurotransmitter involvement.

Abstract: Osmotic and hemodynamic stress are the two primary regulators of vasopressin (VP) release from the posterior pituitary. The pathways providing information about plasma osmolality and blood pressure or blood volume are distinct and utilize different chemical neurotransmitters. Osmotic regulation of VP release is dependent upon afferents from the lamina terminalis region. Glutamate is an important transmitter in this system and angiotensinergic afferents from this region to the VP neurons modulate responses to osmotic challenges. Hemodynamic information is transmitted to the VP neurons via multisynaptic pathways from the brainstem with the A1 catecholamine neurons of the ventrolateral medulla providing the final link for information about decreases in blood pressure and volume. Several neurotransmitters and neuropeptides are expressed in the A1 neurons including norepinephrine (NE), ATP, neuropeptide Y, and substance P. The impact of co-release of these agents on VP release is reviewed and the potential phy...

Pituitary-adrenal activity in acute and chronically stressed male and female mice lacking the 5-HT-3A receptor.

Abstract: The serotonin (5-HT)-3A receptor has been localized in limbic and brainstem structures that regulate hypothalamic–pituitary–adrenal (HPA) activity. We previously showed that 5-HT-3A receptor knock-out (KO) male mice displayed lower ACTH responses to acute restraint or lipopolysaccharide administration compared to age-matched wild-type (WT) males. In the present study, we found that pituitary–adrenal responses to acute stress were not different in female WT and KO mice. Furthermore, we examined the role of the 5-HT-3A receptor in regulation of chronic stress-induced HPA activity in both male and female WT and KO mice. The results show that ACTH, but not corticosterone, responses to novel restraint are lower in chronically cold stressed females compared to non-stressed control females but no effect of 5-HT-3A receptor deletion was observed. In contrast, male mice showed facilitated responses to novel restraint after chronic cold stress and this facilitation produced sex differences in ACTH responses to nove...

The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

Abstract: Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or chronic stress also induced a long term anxiolytic effect, which was also not affected by ADTN lesion.

Non-specific effect of fear conditioning and specific effect of social defeat on social recognition memory performance in female rats.

Abstract: The so called “emotion learning” literature describes the ability of distressing and aversive unconditioned stimuli to classically condition a learned avoidance response. In order to investigate the impact of experience with noxious stimuli in one conditioning context on learning and memory performance in a separate, non-aversively motivated task, juvenile recognition ability was examined in adult female rats exposed previously to one of two environmental stressors. In particular, experimental adult rats were either socially defeated by exposure to an aggressive conspecific rat or fear conditioned using single or multiple pairings with footshock prior to performance of the social recognition task. Experiment 1 established that repeated exposure to a single juvenile resulted in social memory formation reflected in decreased social investigation from the first to the second exposure. Experiment 2 documented that both single and multiple pairings of an environment with footshock produced robust freezing beha...

Effect of stress induced by electrical stimulation of the hypothalamus on the electrical stability of the heart in rabbits.

Abstract: The influence of stress on cardiac electrical stability (CES) and chaotic dynamics of the electrical activity of the heart was studied in acute and chronic experiments in rabbits. Stress was caused by 2–3 h daily immobilization of the animals with electrical stimulation of emotiogenic centers of the hypothalamus through implanted electrodes. CES was estimated by the thresholds for ventricular arrhythmia: paroxysmal ventricular tachycardia, repeated ventricular extrasystoles and ventricular fibrillation (VF). The results showed: (i) CES in stressed rabbits was decreased significantly (p<0.05) compared with controls; (ii) the level of chaos at the onset of VF in stressed rabbits was increased significantly (p<0.05) compared with controls; (iii) heart rate of stressed rabbits was significantly (p<0.05) greater than in controls; (iv) changes in CES parameters depended on whether stress was acute or chronic; (v) acute stress promoted transition of spontaneously reversible VF into spontaneously irreversible VF....

11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Medial Vestibular Nucleus and Cerebellum after Unilateral Vestibular Deafferentation in the Rat

Abstract: In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11beta-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11beta-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11beta-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11beta-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11beta-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.