Stress Response In Animals Research Articles

Small molecule melanin‐concentrating hormone receptor 1 (MCH1R) antagonists as anxiolytic and antidepressive agents

AbstractThe search for new anxiolytics and antidepressants with a more rapid onset of action has led researchers to pursue neuropeptide receptors as molecular targets for these indications. Among these peptide targets, melanin‐concentrating hormone (MCH) has shown promising, albeit inconsistent, data supporting a role for this peptide in human emotional disorders. Neurochemical and neuroanatomical studies have revealed that MCH plays a key role in animal feeding and other behavior; however, alteration of MCH signaling by transgenesis or treatment with endogenous and synthetic MCH1R ligands has produced confounding results in animal models of human emotional disorders. This review describes recent contributions to the understanding of the role of MCH in animal stress response. Drug Dev. Res. 65:291–300, 2005. © 2005 Wiley‐Liss, Inc.

Leukocyte coping capacity: a novel technique for measuring the stress response in vertebrates.

Methods used to quantify the stress response in animals are vital tools in many areas of biology. Here we describe a new method of measuring the stress response, which provides rapid results and can be used in the field or laboratory. After a stressful event, we measure the capacity of circulating leukocytes to produce a respiratory burst in vitro in response to challenge by phorbol myristate acetate (PMA). During the respiratory burst leukocytes produce oxygen free radicals, and the level of production can be measured directly as chemiluminescence. When in vitro PMA-stimulated whole blood chemiluminescence is measured directly after a stressful event, we define the response as the leukocyte coping capacity (LCC). In an experiment badgers (Meles meles), which were caught as part of an on-going population study, were either transported to a central site prior to blood sampling or blood was collected at their site of capture. Transported animals had a significantly lower LCC and showed changes in leukocyte composition that were indicative of stress. We conclude that the stress of transport reduced LCC in badgers and that LCC serves as a quantitative measure of stress. Potential applications of this method are discussed.

Stronger endocrine responses after brief psychological stress in women at familial risk of breast cancer

Recent research has linked exposure to chronic stress to altered acute stress responses and suggests a sensitizing effect of chronic stress leading to a stronger endocrine and cardiovascular response to acute stressors. Substantial evidence indicates that familial breast cancer risk is a chronic life stressor with higher levels of self reported distress. In this study, we investigated whether the endocrine response to a brief psychological stressor was stronger for women at familial risk for breast cancer. Thirty-six women at normal risk of breast cancer (FR− Stress Group) and 17 women at familial risk (FR+ Stress Group) underwent a brief psychological laboratory stress test (speech task and mental arithmetic) over a 15 min period. Thirty women at normal risk not subjected to the stressful task served as controls (FR− Control Group). Plasma epinephrine, norepinephrine and cortisol were measured at baseline, directly after the stress test (15 min) and at 30 min and 45 min post baseline. Heart rate data confirmed the effectiveness of the stress regimen. While there were no significant baseline group differences in the endocrine parameters, the response curves for the familial risk group revealed stronger epinephrine and cortisol reactivity to the stress test, as confirmed by significant group by time interactions. Norepinephrine levels showed a similar pattern, but results did not reach significance. These findings are in line with previous research documenting the facilitating effects of chronic stressors on acute stress response in animals and humans and provide the first evidence in the literature of a heightened endocrine reactivity to acute psychological stress in women at familial risk of breast cancer. The heightened endocrine reactivity to the experimental tasks seen here suggests that these women may experience stronger responses to stressors in their daily lives. According to the recently proposed concept of allostatic load, repeated overly strong stress responses may cumulatively have negative health implications.

Induction of metallothionein in the livers of female Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo- p-dioxin

Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert cytoprotective effects against metal toxicity and external stimuli including ionizing or ultraviolet B irradiation. Since 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is known to cause an exaggerated oxidative stress response in animals and in different organs, we have studied possible involvement of MT in the oxidative responses induced by TCDD. Female Sprague-Dawley (SD) rats (6-week old) were administered a single oral dose of TCDD that varied from 1.0 to 4.0 μg/kg body weight. The serum and tissues were collected 7 days after dosing. Indicators of oxidative damage were assessed. Significant increases in serum 8-hydroxydeoxyguanosine (8-OHdG) levels were observed in the rats dosed with 2.0 and 4.0 μg TCDD/kg bw. Only 4.0 μg TCDD/kg bw produced a decrease in reduced glutathione concentration in the liver. Immunohistochemical staining revealed a TCDD-induced increase in heme oxygenase-1 (HO-1) expression in the hepatic macrophages (Kupffer cells). Under these conditions, MT protein as well as the mRNAs of MT-I and MT-II, were dose-dependently induced in the liver by TCDD doses from 1.0 μg/kg bw. TCDD-induced MT was found to localize in the parenchymal cells of the liver. Serum concentrations of cytokines (TNF-α, IL-1β and IL-6) were not affected by TCDD. The hepatic concentrations of Cu, Zn and Fe were all increased significantly by TCDD administration. Our results suggest that MT levels are increased in the liver upon exposure to TCDD, perhaps by TCDD-generated reactive oxygen species, and that it may play a protective role in TCDD-induced oxidative stress responses as an antioxidant.

A positron emission tomography study of benzodiazepine receptors in post-traumatic stress disorder

Introduction: Post traumatic stress disorder (PTSD) is a common psychiatric disorder among individuals exposed to traumatic experiences with a lifetime prevalence of 8%. Among veterans of war the lifetime prevalence is 22–30%. Neurobiological studies have identified indirect evidence of neuroreceptor and neuro-endocrine abnormalities. The GABA-Benzodiazepine receptor complex is of particular interest as it is an important modulator of stress responses in animals and humans, and it has been shown to have a central role in other anxiety disorders such as Panic Disorder. Positron Emission Tomography (PET) has recently been used to estimate the density of GABA-BZD receptors (Bmax) and the affinity of these receptors (Kd) in vivo using the BZD antagonist PET ligand [11C]-flumazenil.This current study aims to compare the Bmax and Kd of BZD receptors in subjects with PTSD and normal control subjects.Methods: 13 male subjects with war-related PTSD and 13 age and sex matched controls between the ages of 44 and 65 ...

Endocrine and other responses to acute administration of cannabinoid compounds to non-stressed male calves

There is an abundance of cannabinoid (CB) receptors for derivatives of cannabis plants in the brain and throughout the body, and several naturally occurring arachidonic acid derivatives can activate these receptors. The specific objective of this study was to activate these CB receptors in castrated male calves through administration of several CB agonists and to measure immediate changes in concentrations of several serum hormones, respiration rate, and sensitivity to pain. The rationale for the study was that exogenous activation of CB receptors might reveal whether the endogenous CB system (consisting of receptors and endogenous ligands) plays a role in the stress response of animals and specifically whether the activated CB system might be part of a coping mechanism to combat stress. Intravenous administration of three CB agonists (anandamide, methanandamide and WIN 55212-2) to nine castrated male calves under nonstress conditions provoked immediate increases of serum cortisol and respiration rate as well as rapidly caused hypoalgesia to cutaneous pain and thermal stimuli. Although anandamide and methanandamide did not affect serum prolactin, administration of another CB agonist (WIN 55212-2) did increase serum prolactin abruptly. None of the CB agonists affected serum growth hormone. In summary, many of the changes following administration of CB agonists were similar to a stress response in this species, but there were some agonist-specific differences, notably regarding prolactin secretion, as well as differences between calves and observations made in other species. Although CB receptors in calves may be activated by endogenous ligands during exposure to some stressors, the present results are also consistent with this CB system being part of a coping mechanism that helps animals deal with imposed stressors.

Activation of heat shock factor 1 in rat brain during cerebral ischemia or after heat shock.

Recently, many studies have demonstrated the induction of stress proteins in the mammalian nervous system under various pathological conditions. These altered genetic programs may function to protect individual cells against stressful conditions. However, little is known about the molecular mechanisms regulating these stress responses in animals. We report here the activation of a heat shock factor (HSF) in the rat brain during cerebral ischemia or after heat shock. Gel mobility shift assays revealed an increase in DNA binding activity to the heat shock element (HSE) during the early phases of ischemia. Supershift experiments using specific antisera against HSF1 and HSF2 showed that the ischemia-induced HSE-binding activity was mainly due to HSF1. In the heat-shocked brain, HSF1 was also activated, and the HSE-binding activity was higher in the cerebellum than in the cerebral cortex or hippocampus; Western blot analysis also showed that HSF1 was more abundant in the cerebellum than in the other two brain regions. Our results indicate that heat shock gene transcription is regulated by the activation of HSF1 in both cerebral ischemia and heat shock, and that different brain regions display differential sensitivities in their stress response. The cellular signals for heat shock gene transcription under in vivo pathological conditions will also be discussed.

Restraint stress in biomedical research: An update

Since the publication of our initial review of restraint stress in 1986, much work has continued with this technique, either as a tool for the investigation of other pharmacological, physiological, or pathologic phenomena or with restraint stress itself serving as the object of the study. As we noted in 1986, the major use of restraint has been for the induction of stress responses in animals and, more specifically, for the investigation of drug effects, particularly as they affect typical stress-related pathology—gastrointestinal, neuroendocrine, and immunological agents have been extensively studied. In compiling this update on restraint stress and its effects, we noted an increasing emphasis on central nervous system mechanisms in peripheral disease, especially gastrointestinal disease. In particular, many CNS-active agents have been tested for their effects on gastric and duodenal lesion formation and gastric secretion, including antidepressants, antipsychotics, anxiolytics, noradrenergic, serotonergic, dopaminergic, and peptidergic compounds. Some of these agents are especially active in the gastrointestinal tract even when administered centrally, further solidifying the concept of a brain-gut axis. The present update includes studies of: methods and procedures, prerestraint manipulations, postrestraint/healing effects, and drug effects. In addition, a current bibliography of reports that have employed restraint is included.

Modification of pituitary-adrenal feedback sensitivity in young rats by neonatal treatment with cortisol.

Neonatal exposure of rats to cortisol acetate was found to alter pituitary-adrenal feedback regulation at 20-25 days of age. Plasma levels of adrenocorticotrophin (ACTH) after ether stress were reduced in cortisol-treated rats pre-treated with 100 microgram corticosterone/100 g body weight, while rats given vehicle neonatally did not show suppression of the ACTH response below levels in animals given saline only or not injected as pre-treatments. Neonatal cortisol increased sensitivity to dexamethasone in inhibition of the stress response; cortisol-treated animals had a reduced plasma corticosterone response to stress 3 h after pre-treatment with 1.25, 2.5, 25, or 250 microgram dexamethasone/100 g body weight, while the stress response in animals given vehicle neonatally was not inhibited by the lowest dosage of dexamethasone. Neonatal cortisol treatment did not affect corticosteroid-binding globulin (CBG) binding capacity in plasma of 25-day-old animals. Thus, neonatal treatment with cortisol appears to increase feedback sensitivity to circulating corticosteroids at 20-25 days of age.