Showing papers on "Chronic stress published in 2007"
TL;DR: As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
Abstract: The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load"). Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis"). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
3,062 citations
TL;DR: A meta-analysis showed that much of the variability in HPA activity is attributable to stressor and person features, as hormonal activity is elevated at stressor onset but reduces as time passes.
Abstract: The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.
2,196 citations
TL;DR: A theoretical model of Reward Based Stress Eating is proposed, which emphasizes the role of cortisol and reward circuitry on motivating calorically dense food intake, and elucidating potential neuroendocrine mediators in the relationship between stress and eating.
1,485 citations
TL;DR: The results suggest that the vertebrate ATF6alpha pathway evolved to maintain ER function when cells are challenged with chronic stress and provide a rationale for the overlap among the three UPR pathways.
635 citations
TL;DR: Large differences have been found across species, breeds and individuals, which reflect the contribution of genetic factors and environmental influences, especially during development, in HPA axis functioning.
633 citations
TL;DR: It is demonstrated that short periods of stress exposure induce spatial reference memory deficits before affecting PFC-dependent tasks, thus suggesting that the impairment of synaptic plasticity within the hippocampus-to-PFC connection is of relevance to the stress-induced PFC dysfunction.
Abstract: Research on the detrimental effects of stress in the brain has mainly focused on the hippocampus. Because prefrontal cortex (PFC) dysfunction characterizes many stress-related disorders, we here analyzed the impact of chronic stress in rats on the integrity of the hippocampal-PFC pathway, monitored by behavioral and electrophysiological function and morphological assessment. We show that chronic stress impairs synaptic plasticity by reducing LTP induction in the hippocampal-PFC connection; in addition, it induces selective atrophy within the PFC and severely disrupts working memory and behavioral flexibility, two functions that depend on PFC integrity. We also demonstrate that short periods of stress exposure induce spatial reference memory deficits before affecting PFC-dependent tasks, thus suggesting that the impairment of synaptic plasticity within the hippocampus-to-PFC connection is of relevance to the stress-induced PFC dysfunction. These findings evidence a fundamental role of the PFC in maladaptive responses to stress and identify this area as a target for intervention in stress-related disorders.
548 citations
TL;DR: Data emphasize the impact of PS on both fetal growth and endocrine function as well as on placental physiology, suggesting that PS could program processes implied in adult biology and pathophysiology.
Abstract: Prenatal stress (PS) can cause early and long-term developmental effects resulting in part from altered maternal and/or fetal glucocorticoid exposure. The aim of the present study was to assess the impact of chronic restraint stress during late gestation on feto-placental unit physiology and function in embryonic (E) day 21 male rat fetuses. Chronic stress decreased body weight gain and food intake of the dams and increased their adrenal weight. In the placenta of PS rats, the expression of glucose transporter type 1 (GLUT1) was decreased, whereas GLUT3 and GLUT4 were slightly increased. Moreover, placental expression and activity of the glucocorticoid "barrier" enzyme 11beta-hydroxysteroid dehydrogenase type 2 was strongly reduced. At E21, PS fetuses exhibited decreased body, adrenal pancreas, and testis weights. These alterations were associated with reduced pancreatic beta-cell mass, plasma levels of glucose, growth hormone, and ACTH, whereas corticosterone, insulin, IGF-1, and CBG levels were unaffected. These data emphasize the impact of PS on both fetal growth and endocrine function as well as on placental physiology, suggesting that PS could program processes implied in adult biology and pathophysiology.
380 citations
TL;DR: One of the challenges for future research is to link the cellular changes seen in animal models for chronic stress to behavioral effects and to understand the risks they can impose on humans for the precipitation of stress-related disorders.
355 citations
TL;DR: It is found that chronic antidepressant administration reversed the decrease in cortical cell proliferation, as well as the deficit in sucrose preference, and this effect was dependent on the duration, intensity and type of stress, and was region-specific.
317 citations
TL;DR: The results showed that only rats exposed to the 6 h/21 days restraint paradigm exhibited CA3 apical dendritic retraction, consistent spatial memory deficits, and decreased body weight gain compared to experimental counterparts and controls, which support the interpretation that chronic psychological stress produces hippocampal-dependent cognitive deficits that are consistent with hippocampal structural changes.
300 citations
TL;DR: It is speculated that chronic-stress-related variations in brain morphology are reciprocally and functionally related to adaptive and maladaptive changes in cognition, neuroendocrine activity, and psychiatric vulnerability.
TL;DR: Investigation of chronic psychological stress in female European starlings showed sensitization of the CORT response to acute stress, which is a physiological change that could persist to adulthood, suggesting that more research is necessary before CORT concentrations can be used to accurately assess chronic stress in field studies.
TL;DR: The results suggested that curcumin administration increased hippocampal neurogenesis in chronically stressed rats, similar to classic antidepressant imipramine treatment, and demonstrated that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers.
TL;DR: The findings corroborate recent primate studies with induced stress, and suggest that hair cortisol is a potential biomarker of chronic stress in pregnancy.
Abstract: Purpose: Stress has been shown to cause a large range of adverse fetal effects. This pilot study is the first attempt to examine cortisol level in the hair of pregnant women and assess its potential as a biomarker of gestational stress.
Patients and Methods: Twenty-five healthy pregnant women, in whom hair cortisol levels and the Perceived Stress Scale (PSS) were measured and correlated.
Results: Maternal hair cortisol levels, ranging between 0.06 and 0.23 nmol/g of hair correlated positively and significantly with measures of perceived stress (ranging between 2-22); (Rs=0.47) (P < 0.05).
Conclusions: Our findings corroborate recent primate studies with induced stress, and suggest that hair cortisol is a potential biomarker of chronic stress in pregnancy. This new long term biological marker may have important implications in research and clinical practice.
TL;DR: Exposure to chronic variable stress increased basal plasma corticosterone levels and that both, chronic restraint and variable stresses, promote higher cortic testosterone levels in response to a novel environment, but not to a challenge restraint stress, as compared to the control (non-stressed) group.
TL;DR: It is concluded that, contrary to other compounds interfering with the effects of chronic stress on neurogenesis, like antidepressants, the normalizing effects of mifepristone on Neurogenesis are rapid and particularly potent in a high stress environment.
Abstract: In rodents, stress suppresses adult neurogenesis. This is thought to involve activation of glucocorticoid receptors in the brain. In the present study, we therefore questioned whether glucocorticoid receptor blockade by mifepristone can normalize the effects of chronic stress on adult neurogenesis. Rats received mifepristone on the last 4 days of a 21-day chronic unpredictable and inescapable stress regimen. Neurogenesis was analysed by stereological quantification of adult-generated cell survival (bromodeoxyuridine), young neuronal survival (doublecortin) and cell proliferation (Ki-67). The results show that only 4 days of mifepristone treatment normalized the stress-induced reductions in neurogenesis. Importantly, mifepristone by itself had no effect on neurogenesis. We conclude that, contrary to other compounds interfering with the effects of chronic stress on neurogenesis, like antidepressants, the normalizing effects of mifepristone on neurogenesis are rapid and particularly potent in a high stress environment. This neurogenic action of mifepristone could potentially contribute to its clinical mechanism of action.
TL;DR: In this article, a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet), was administered with 50, 120, or 200 microg/kg/d of dexamethasone (dex50, dex120, or dex200) from mid-term to infants.
Abstract: Prenatal stress or glucocorticoid administration has persisting "programming" effects on offspring in rodents and other model species. Multiple doses of glucocorticoids are in widespread use in obstetric practice. To examine the clinical relevance of glucocorticoid programming, we gave 50, 120, or 200 microg/kg/d of dexamethasone (dex50, dex120, or dex200) orally from mid-term to a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet). Dexamethasone dose-dependently reduced maternal cortisol levels without effecting maternal blood pressure, glucose, electrolytes, or weight gain. Birth weight was unaffected by any dexamethasone dose, although postnatal growth was attenuated after dex120 and dex200. At 8 months of age, dex120 and dex200 offspring showed impaired glucose tolerance and hyperinsulinemia, with reduced (approximately 25%) pancreatic beta cell number at 12 months. Dex120 and dex200 offspring had increased systolic and diastolic blood pressures at 12 months. Mild stress produced an exaggerated cortisol response in dex200 offspring, implying hypothalamic-pituitary-adrenal axis programming. The data are compatible with the extrapolation of the glucocorticoid programming hypothesis to primates and indicate that repeated glucocorticoid therapy and perhaps chronic stress in humans may have long-term effects.
TL;DR: A novel chronic social stress paradigm in male mice during adolescence results in persistent alterations of hypothalamus-pituitary-adrenal axis function and behavior, which are reversible by pharmacological treatment and allows to investigate the interaction of genetic susceptibility and environmental risk factors.
TL;DR: It is suggested that nNOS over‐expression in the hippocampus is essential for chronic stress‐induced depression and inhibiting nN OS signaling in brain may represent a novel approach for the treatment of depressive disorders.
Abstract: Increasing evidence suggests that depression may be associated with a lack of hippocampal neurogenesis. It is well established that neuronal nitric oxide synthase (nNOS)-derived NO exerts a negative control on the hippocampal neurogenesis. Using genetic and pharmacological methods, we investigated the roles of nNOS in depression induced by chronic mild stress (CMS) in mice. Hippocampal nNOS over-expression was first observed 4 days and remained elevated 21 and 56 days after exposure to CMS. The mice exposed to CMS exhibited behavioral changes typical of depression, and impaired neurogenesis in the hippocampus. The CMS-induced behavioral despair and hippocampal neurogenesis impairment were prevented and reversed in the null mutant mice lacking nNOS gene (nNOS-/-) and in the mice receiving nNOS inhibitor. Disrupting hippocampal neurogenesis blocked the antidepressant effect of nNOS inhibition. Moreover, nNOS-/- mice exhibited antidepressant-like properties. Our findings suggest that nNOS over-expression in the hippocampus is essential for chronic stress-induced depression and inhibiting nNOS signaling in brain may represent a novel approach for the treatment of depressive disorders.
TL;DR: Chronic exposure to CSC alters relevant neuronal, neuroendocrine and immune functions that could be directly or indirectly involved in the damage of the histological integrity of the colon comparable with that seen during the development of colitis.
Abstract: We investigated chronic psycho-social stress effects on stress-related parameters and on pathohistological changes in the murine colon. Moreover, we aimed to reveal the involvement of adrenal glucocorticoids in chronic stress effects. Chronic subordinate colony housing (CSC, 19 d) resulted in reduced body weight gain, thymus atrophy, adrenal hypertrophy, increased plasma norepinephrine, and increased anxiety. With respect to the time course of CSC effects, CRH mRNA in the hypothalamic paraventricular nucleus, light phase corticosterone and tyrosine hydroxylase expression in colonic tissue were found to be increased, whereas tyrosine hydroxylase expression in the locus coeruleus was found to be decreased on d 2 of CSC; these parameters returned to control levels thereafter. Nevertheless, after 19 d of CSC exposure, the adrenal corticosterone responses in vivo and in vitro, and glucocorticoid sensitivity of isolated splenic cells were found to be decreased. Importantly, in CSC mice a significant histological damage of the colon was found beginning on d 14 of CSC exposure. Additionally, pro- and antiinflammatory cytokine secretion by mesenteric lymph node cells was increased after CSC exposure. Adrenalectomy before CSC at least partially prevented these chronic stress effects as reflected by less increase in proinflammatory cytokine secretion and an equal histological damage score in adrenalectomized compared with sham-operated CSC mice. In conclusion, chronic exposure to CSC alters relevant neuronal, neuroendocrine and immune functions that could be directly or indirectly involved in the damage of the histological integrity of the colon comparable with that seen during the development of colitis.
TL;DR: Hair cortisol is influenced by days of ventilation in NICU term infants, a potentially valid outcome for chronic neonatal stress in these infants and warrants further investigation.
Abstract: Background: As preterm and term infants in the neonatal intensive care unit (NICU) undergo multiple stressful/painful procedures, research is required that addresses chronic stress.
TL;DR: In this article, the effects of chronic stress on cognition and anxiety were investigated in a more diverse population (age-and sex-wise) at least in relation to the neural functions of cognition.
Abstract: Cognitive responses to stress follow the temporally dependent pattern originally established by Selye (1) wherein short-term stressors elicit adaptive responses whereas continued stress (chronic) results in maladaptive changes--deleterious effects on physiological systems and impaired cognition. However, this pattern for cognitive effects appears to apply to only half the population (males) and, more specifically, to young, adult males. Females show different cognitive responses to stress. In contrast to impaired cognition in males after chronic stress, female rodents show enhanced performance on the same memory tasks after the same stress. Not only cognition, but anxiety, shows sex-dependent changes following chronic stress--stress is anxiolytic in males and anxiogenic in females. Moreover, behavioral responses to chronic stress are different in developing as well as aging subjects (both sexes) as compared to adults. In aged rats, chronic stress enhances recognition memory in both sexes, does not alter spatial memory, and anxiety effects are opposite to young adults. When pregnant dams are exposed to chronic stress, at adulthood the offspring display yet different consequences of stress on anxiety and cognition, and, in contrast to adulthood when the behavioral effects of stress are reversible, prenatal stress effects appear enduring. Changing levels of estradiol in the sexes over the lifespan appear to contribute to the differences in response to stress. Thus, theories of stress dependent modulations in CNS function--developed solely in male models, focused on peripheral physiological processes and tested in adults--may require revision when applied to a more diverse population (age- and sex-wise) at least in relation to the neural functions of cognition and anxiety. Moreover, these results suggest that other stressors and neural functions should be investigated to determine whether age, sex and gonadal hormones also have an impact.
TL;DR: The proposed mechanisms implicated in neuroplasticity impairments that result from stress and that contribute to mood disorders are discussed, with a particular interest in adult neurogenesis and gliogenesis.
Abstract: Structural and morphological changes in limbic brain regions are associated with depression, chronic stress and antidepressant treatment, and increasing evidence supports the hypothesis that dysregulation of cell proliferation contributes to these effects. We review the morphological alterations observed in two brain regions implicated in mood disorders, the prefrontal cortex and hippocampus, and discuss the similarities and differences of the cellular consequences of chronic stress. We briefly discuss the proposed mechanisms implicated in neuroplasticity impairments that result from stress and that contribute to mood disorders, with a particular interest in adult neurogenesis and gliogenesis. This information has contributed to novel antidepressant medication development that utilizes adult neurogenesis and gliogenesis as preclinical cellular markers for predicting antidepressant properties of novel compounds.
Journal Article•
TL;DR: This paper will provide a brief overview of what is known about the endocrine responses to stressors and the catecholamines, epinephrine and norepinephrine and the glucocorticoids help to orchestrate the body's stress response.
Abstract: When an animal detects a stressor, it initiates a stress response. The physiological aspects of this stress response are mediated through two endocrine systems. The catecholamine hormones epinephrine and norepinephrine are released from the adrenal medulla very rapidly and have numerous effects on behavior, metabolism, and the cardiovascular system. This is commonly termed the Fight-or-Flight response. On a longer time scale, the glucocorticoid hormones are released from the adrenal cortex. They interact with intracellular receptors and initiate gene transcription. This production of new proteins means that glucocorticoids have a delayed, but more sustained, effect than the catecholamines. The glucocorticoids orchestrate a wide array of responses to the stressor. They have direct effects on behavior, metabolism and energy trafficking, reproduction, growth, and the immune system. The sum total of these responses is designed to help the animal survive a short-term stressful stimulus. However, under conditions of long-term stress, the glucocorticoid-mediated effects become maladaptive and can lead to disease. Stress, as originally coined by Selye (1946), has been the subject of study for decades. It became quickly apparent that the term “stress” actually encompasses three related topics: changes/stimuli from the environment that cause “stress” (subsequently called stressors); the physiological and psychological responses to those stimuli (subsequently called the stress response); and the diseases that result from an overstimulation of the physiological and psychological responses (subsequently called chronic stress effects). Research has focused on all three of these concepts. An enormous amount is now known about what stimuli elicit which physiological and psychological responses. We also know many of the mechanisms whereby various hormonal mediators compromise organ, tissue, and cellular function (Fink, 2007). This paper will provide a brief overview of what is known about the endocrine responses to stressors. The following general information is broadly known and widely presented. Most of the information comes from the following sources (McEwen & Goodman, 2001; Nelson, 2005; Norman & Litwack, 1997; Norris, 2007; Sapolsky, Romero, & Munck, 2000) and interested readers should consult them for more detail. Specific information and individual studies are cited independently. Although there are many hormones that have been identified as playing a role in the vertebrate stress response, two categories of hormones are thought to form the central components of the endocrine response. These are the catecholamines, epinephrine and norepinephrine (also known as adrenalin and noradrenalin) and the glucocorticoids. Together, these hormones help to orchestrate the body’s stress response. How they do so is presented below.
TL;DR: CORT levels in response to a potentially mild stressor stayed at basal levels and failed to differ among key groups, supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations.
Abstract: We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 microg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer's disease, and Cushing's disease.
TL;DR: It is shown that stress hormones such as norepinephrine lead to increased expression of IL-6 mRNA and protein levels in ovarian carcinoma cells and that norpinephrine stimulation activates Src tyrosine kinase and this activation is required for increased IL- 6 expression.
TL;DR: It is found that hippocampal tau-P elicited by an acute emotional stressor, restraint, was not affected by preventing the stress-induced rise in glucocorticoids but was blocked by genetic or pharmacologic disruption of signaling through the type 1 corticotropin-releasing factor receptor (CRFR1).
Abstract: Hyperphosphorylation of the microtubule-associated protein tau is a key event in the development of Alzheimer's disease (AD) neuropathology. Acute stress can induce hippocampal tau phosphorylation (tau-P) in rodents, but the mechanisms and pathogenic relevance of this response are unclear. Here, we find that hippocampal tau-P elicited by an acute emotional stressor, restraint, was not affected by preventing the stress-induced rise in glucocorticoids but was blocked by genetic or pharmacologic disruption of signaling through the type 1 corticotropin-releasing factor receptor (CRFR1). Conversely, these responses were exaggerated in CRFR2-deficient mice. Parallel CRFR dependence was seen in the stress-induced activation of specific tau kinases. Repeated stress exposure elicited cumulative effects on tau-P and its sequestration in an insoluble, and potentially pathogenic, form. These findings support differential regulatory roles for CRFRs in an AD-relevant form of neuronal plasticity and may link datasets documenting alterations in the CRF signaling system in AD and implicating chronic stress as a risk factor in age-related neurological disorders.
TL;DR: It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopremolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression.
TL;DR: The importance of the neuroendocrine stress response in tumor biology is highlighted and mechanisms by which the β-adrenergic receptors on ovarian cancer cells enhance angiogenesis and tumor growth are discussed.
Abstract: Behavioral processes have long been suspected to influence many health processes including effects on cancer. However, mechanisms underlying these observations are not fully understood. Recent work has demonstrated that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden, and a more invasive pattern of ovarian cancer growth in an orthotopic mouse model. These effects are mediated primarily through the beta(2) adrenergic receptor (ADRB2) activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway. Additionally, tumors in stressed animals have increased vascularization and enhanced expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) -2 and -9. In this review, we highlight the importance of the neuroendocrine stress response in tumor biology and discuss mechanisms by which the beta-adrenergic receptors on ovarian cancer cells enhance angiogenesis and tumor growth.
TL;DR: The data suggest that the Avpr1b is required for the normal pituitary and adrenal response to some acute stressful stimuli and is necessary only for a normal ACTH response during chronic stress.
Abstract: The role of arginine vasopressin (Avp) as an ACTH secretagogue is mediated by the Avp 1b receptor (Avpr1b) found on anterior pituitary corticotropes. Avp also potentiates the actions of CRH (Crh) and appears to be an important mediator of the hypothalamic-pituitary-adrenal axis response to chronic stress. To investigate the role of Avp in the hypothalamic-pituitary-adrenal axis response to stress, we measured plasma ACTH and corticosterone (CORT) levels in Avpr1b knockout (KO) mice and wild-type controls in response to two acute (restraint and insulin administration) and one form of chronic (daily restraint for 14 d) stress. No significant difference was found in the basal plasma levels of ACTH and CORT between the two genotypes. Acute restraint (30 min) increased plasma ACTH and CORT to a similar level in both the Avpr1b mutant and wild-type mice. In contrast, plasma ACTH and CORT levels induced by hypoglycemia were significantly decreased in the Avpr1b KO mice when compared with wild-type littermates. There was no difference in the ACTH response to acute and chronic restraint in wild-type mice. In the Avpr1b KO group subjected to 14 sessions of daily restraint, plasma ACTH was decreased when compared with wild-type mice. On the other hand, the CORT elevations induced by restraint did not adapt in the Avpr1b KO or wild-type mice. The data suggest that the Avpr1b is required for the normal pituitary and adrenal response to some acute stressful stimuli and is necessary only for a normal ACTH response during chronic stress.