Effects of acupuncture on behavioral, cardiovascular and hormonal responses in restraint-stressed Wistar rats

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Guimarães C.M.

1997-01-01

Full Text Available Stress is a well-known entity and may be defined as a threat to the homeostasis of a being. In the present study, we evaluated the effects of acupuncture on the physiological responses induced by restraint stress. Acupuncture is an ancient therapeutic technique which is used in the treatment and prevention of diseases. Its proposed mechanisms of action are based on the principle of homeostasis. Adult male Wistar EPM-1 rats were divided into four groups: group I (N = 12, unrestrained rats with cannulas previously implanted into their femoral arteries for blood pressure and heart rate measurements; group II (N = 12, rats that were also cannulated and were submitted to 60-min immobilization; group III (N = 12, same as group II but with acupuncture needles implanted at points SP6, S36, REN17, P6 and DU20 during the immobilization period; group IV (N = 14, same as group III but with needles implanted at points not related to acupuncture (non-acupoints. During the 60-min immobilization period animals were assessed for stress-related behaviors, heart rate, blood pressure and plasma corticosterone, noradrenaline and adrenaline levels. Group III animals showed a significant reduction (60% on average, P<0.02 in restraint-induced behaviors when compared to groups II and IV. Data from cardiovascular and hormonal assessments indicated no differences between group III and group II and IV animals, but tended to be lower (50% reduction on average in group I animals. We hypothesize that acupuncture at points SP6, S36, REN17, P6 and DU20 has an anxiolytic effect on restraint-induced stress that is not due to a sedative action

Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain

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Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory

2009-01-01

Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017

Exposure of pregnant rats to uranium and restraint stress: Effects on postnatal development and behavior of the offspring

International Nuclear Information System (INIS)

Sanchez, Domenec J.; Belles, Montserrat; Albina, Maria L.; Gomez, Mercedes; Linares, Victoria; Domingo, Jose L.

2006-01-01

The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2 h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24 h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited

Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats

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Nakade, Yukiomi; Mantyh, C.; Pappas, T.N.; Takahashi, Toku

2007-01-01

Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. Immediately after intracisternal injection of CRF, 51 Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after 51 Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of 51 Cr was calculated. For the restraint stress study, after administration of 51 Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output. (author)

Effect of chronic restraint stress on inhibitory gating in the auditory cortex of rats.

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Ma, Lanlan; Li, Wai; Li, Sibin; Wang, Xuejiao; Qin, Ling

2017-05-01

A fundamental adaptive mechanism of auditory function is inhibitory gating (IG), which refers to the attenuation of neural responses to repeated sound stimuli. IG is drastically impaired in individuals with emotional and cognitive impairments (i.e. posttraumatic stress disorder). The objective of this study was to test whether chronic stress impairs the IG of the auditory cortex (AC). We used the standard two-tone stimulus paradigm and examined the parametric qualities of IG in the AC of rats by recording the electrophysiological signals of a single-unit and local field potential (LFP) simultaneously. The main results of this study were that most of the AC neurons showed a weaker response to the second tone than to the first tone, reflecting an IG of the repeated input. A fast negative wave of LFP showed consistent IG across the sampled AC sites, whereas a slow positive wave of LFP had less IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level, due to the increase in response to the second tone. This study provided new evidence that chronic stress disrupts the physiological function of the AC. Lay Summary The effects of chronic stress on IG were investigated by recording both, single-unit spike and LFP activities, in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities in the AC showed an IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level.

Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

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Saiful Bhari Talip

2013-06-01

Full Text Available Exposure to chronic restraint stress has been shown to cause a number of morphological changes in the hippocampal formation of rats. Tocotrienol, an isoform of vitamin E, exhibits numerous health benefits, different from those of tocopherol. Recent studies have demonstrated that tocotrienol prevents stress-induced changes in the gastric mucosa, thus indicating that it may also protect other organs such as the brain from the damaging effects of stress. Therefore, the aim of the present study was to investigate the protective effect of tocotrienol-rich fraction (TRF extracted from palm oil on the dentate gyrus of rats following exposure to chronic restraint stress. Thirty-six male Sprague Dawley rats were divided into four groups: control, stress, tocotrienol and combination of stress and tocotrienol. Animals were stressed by restraining them for 5 hours every day for 21 consecutive days. TRF was administered via oral gavage at a dose of 200 mg/kg body weight. Our results showed that the plasma corticosterone level was significantly increased in response to stress, compared to the control. The results confirmed previous findings that chronic restraint stress suppresses cellular proliferation and reduces granule cell number in the dentate gyrus. However, TRF supplementation failed to prevent or minimize these stress-induced changes. Therefore, we conclude that TRF at the current dosage is not effective in preventing the morphological changes in the dentate gyrus induced by chronic restraint stress.

Effect of Fluoxetine on the Hippocampus of Wistar Albino Rats in Cold Restraint Stress Model.

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Jayakumar, Saikarthik; Raghunath, Gunapriya; Ilango, Saraswathi; Vijayakumar, J; Vijayaraghavan, R

2017-06-01

Stress has been known to be a potential modulator of learning and memory. Long term stress can lead to depression. Fluoxetine is a selective serotonin reuptake inhibitor group of drug used in the treatment of depression. The present study was conducted to evaluate the potential of Fluoxetine on cold restraint induced stress in the hippocampus of Wistar rats. A total of 18 male wistar albino rats were divided randomly into three groups (n=6). Group 1 was the control group which were kept in normal laboratory conditions. Group 2 was the negative control group which were given cold restraint stress for period of four weeks. Group 3 was the experimental group, where the animals were pretreated with fluoxetine 10 mg/kg for a period of one week followed by cold restraint stress for 30 minutes and cotreated with fluoxetine 10 mg/kg for a period of four weeks. The whole study was done for a period of five weeks followed by behavioural studies and subsequently sacrificed with removal of brain for various histological, Immunohistochemical (IHC), neurochemical and antioxidant analysis. The values were expressed as Mean±SEM. One-way analysis of variance followed by Tukey's multiple comparisons test was used for the comparison of means. A probability of 0.05 and less was taken as statistically significant using Prism Graphpad software version 6.01. The results show there was significant improvement in the Morris water maze test after treatment with fluoxetine in Group 2. Similar results were also noted in the levels of neurotransmitters and antioxidant levels in brain and also in the number of cells counted in IHC and histological studies by H&E when Group 3 was compared with Group 2. The treatment reversed the damage in Group 2 which was comparable with the control group. The results revealed that administration of fluoxetine 10 mg/kg given orally has a potential antistressor effect by improving the neurogenic and neuroprotective effect on the cold restraint stress induced

Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

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Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

2017-03-01

Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

Repeated restraint stress lowers the threshold for response to third ventricle CRF administration.

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Harris, Ruth B S

2017-03-01

Rats and mice exposed to repeated stress or a single severe stress exhibit a sustained increase in energetic, endocrine, and behavioral response to subsequent novel mild stress. This study tested whether the hyper-responsiveness was due to a lowered threshold of response to corticotropin releasing factor (CRF) or an exaggerated response to a standard dose of CRF. Male Sprague-Dawley rats were subjected to 3h of restraint on each of 3 consecutive days (RRS) or were non-restrained controls. RRS caused a temporary hypophagia but a sustained reduction in body weight. Eight days after the end of restraint, rats received increasing third ventricle doses of CRF (0-3.0μg). The lowest dose of CRF (0.25μg) increased corticosterone release in RRS, but not control rats. Higher doses caused the same stimulation of corticosterone in the two groups of rats. Fifteen days after the end of restraint, rats were food deprived during the light period and received increasing third ventricle doses of CRF at the start of the dark period. The lowest dose of CRF inhibited food intake during the first hour following infusion in RRS, but not control rats. All other doses of CRF inhibited food intake to the same degree in both RRS and control rats. The lowered threshold of response to central CRF is consistent with the chronic hyper-responsiveness to CRF and mild stress in RRS rats during the post-restraint period. Copyright © 2016 Elsevier Inc. All rights reserved.

Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats.

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Itoh, Y H; Noguchi, R

2000-01-01

The purpose of this study was to assess the preventive effect of pre-mild whole-body heating (WBH) on gastric ulcer induced by restraint and water-immersion stress. The ulcer index and ulcer area ratio in rats exposed to restraint and water-immersion stress were significantly decreased (p immersion stress alone (p immersion, thereby preventing gastric ulcer formation. Pre-treatment with mild WBH is the safest cytoprotective method through the accumulation of HSP 70f. The concentration of HSP 70f in peripheral lymphocytes may be a useful clinical laboratory indicator for assessing the level of HSP 70f as having cytoprotective activity.

Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

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Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

2004-03-01

Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

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Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

2015-12-01

Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

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Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage

DEFF Research Database (Denmark)

Jorgensen, Anders; Maigaard, Katrine; Wörtwein, Gitta

2013-01-01

acids, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably collect 24h urine samples, the full 3-week restraint stress paradigm was performed in metabolism cages. We further determined frontal...... and Tnf). The metabolism cage housing in itself did not significantly influence a range of biological stress markers. In the restraint stress group, there was a sustained 2.5 fold increase in 24h corticosterone excretion from day 2 after stress initiation. However, neither whole-body nor cerebral measures......Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common mechanism underlying accelerated aging in psychological stress states and mental disorders. In the present study, we measured the urinary excretion of corticosterone and markers of systemic oxidative stress on nucleic...

Restraint Stress Impairs Glucose Homeostasis Through Altered ...

African Journals Online (AJOL)

olayemitoyin

serum level of adiponectin was significantly (p< 0.05) lower compared with ... were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. ... controlled conditions for the light/dark cycle, ..... increase the production of catecholamines. ... specific protein that has been suggested to play a role.

Effect of antioxidant supplementation on lipid peroxidation and antioxidant enzyme activity on exposure to acute restraint stress in sprague dawley rats

International Nuclear Information System (INIS)

Lodhi, G.M.; Hussain, M.M.; Aslam, M.

2012-01-01

To determine the effects of ascorbic acid (AA) and alpha tocopherol (AT) supplementation on stress induced changes in serum malondialdehyde and serum superoxide dismutase levels in male Sprague Dawley rats. Study design: Quasi experimental study Place and Duration of Study: Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March 2009 to September 2009. Materials and Methods: Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group I served as control without stress and group II exposed to restraint stress for 06 hours, group III given ascorbic acid, group IV alpha tocopherol and group V was supplemented with both vitamins along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for six hours. Immediately after stress, the blood samples were analyzed colorimetrically to estimate serum malondialdehyde and superoxide dismutase by commercially available kits. Results: There was no significant fall in serum malondialdehyde in rats supplemented with ascorbic acid alone, however rats supplemented with alpha tocopherol or combination of ascorbic acid and alpha tocopherol revealed significant fall in serum malondialdehyde and increment in superoxide dismutase activity. Conclusions: Alpha tocopherol alone and in combination with ascorbic acid is effective to prevent reactive oxygen species induced increase in lipid peroxidation and fall in super oxide dismutase activity thereby conferring protection against oxidative stress. (author)

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

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Silveira P.P.

2000-01-01

Full Text Available Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment. The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops®. The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 ± 0.44 pellets and midazolam group: 3.60 ± 0.57 pellets. The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 ± 0.44 pellets and stressed group: 4.18 ± 0.58 pellets. Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 ± 0.58 pellets; stressed/midazolam group: 3.2 ± 0.49 pellets. Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect.

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

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Bowman, R E; Ferguson, D; Luine, V N

2002-01-01

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

Glucocorticoid receptors in the basolateral amygdala mediated the restraint stress-induced reinstatement of methamphetamine-seeking behaviors in rats.

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Taslimi, Zahra; Sarihi, Abdolrahman; Haghparast, Abbas

2018-04-21

Methamphetamine (METH) addiction is a growing epidemic worldwide. It is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of the basolateral amygdala (BLA) in effects of stress on the reward pathway has been discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of the extinguished METH-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in eighty-one adult male Wistar rats weighing 220-250 g. The animals received a daily injection of methamphetamine (0.5 mg/kg), during the conditioning phase. In extinction phase, the rats were put in the CPP box for 30 min per day for 8 days. After the extinction, the animals were exposed to acute restraint stress (ARS), 3 h before subcutaneous administration of sub-threshold dose of methamphetamine (0.125 mg/kg), based on our previous study, in reinstatement phase. In separated groups, the rats were exposed to chronic restraint stress (CRS) for 1 h each day during the extinction phase. To block the GRs in BLA, the animals unilaterally received RU38486 as GRs antagonist (10, 30 and 90 ng/0.3 μl DMSO) in all ARS groups on reinstatement day. In separated experiments, RU38486 (3, 10 and 30 ng/0.3 μl DMSO) was microinjected into the BLA in CRS groups prior to exposure to stress every day in extinction phase. The results revealed that intra-BLA RU38486 in ARS (90 ng) and CRS (10 and 30 ng) groups significantly prevented the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via GRs in the BLA. This effect was not quite similar in acute and chronic stress conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

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Petra eSántha

2016-01-01

Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

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Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

2018-01-04

Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Anti-stress effect of ethyl acetate soluble fraction of Morus alba in chronic restraint stress.

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Nade, Vandana S; Yadav, Adhikrao V

2010-09-01

Restraint stress is a well-known method to induce chronic stress which leads to alterations in various behavioral and biochemical parameters. The present work was designed to study anti-stress effects of Morus alba in chronic restraint stress (RS)-induced perturbations in behavioral, biochemical and brain oxidative stress status. The stress was produced by restraining the animals inside an adjustable cylindrical plastic tube for 3 h once daily for ten consecutive days. The ethyl acetate soluble fraction of Morus alba (EASF) 25, 50, 100 mg/kg and diazepam (1 mg/kg) per day was administered 60 min prior to the stress procedure. The behavioral and biochemical parameters such as open field, cognitive dysfunction; leucocytes count; blood glucose and corticosteroid levels were determined. On day 10, the rats were sacrificed and biochemical assessment of superoxide dismutase (SOD), lipid peroxidation (LPO), catalase (CAT), and glutathione reductase (GSH) in whole rat brain were performed. Chronic restraint stress produced cognitive dysfunction, altered behavioral parameters, increased leucocytes count, SOD, LPO, glucose and corticosterone levels, with concomitant decrease in CAT and GSH activities. Gastric ulceration, adrenal gland and spleen weights were also used as the stress indices. All these RS induced perturbations were attenuated by EASF of Morus alba. The results of the study suggest that in addition to its classically established pharmacological activities, the plant also has immense potential as an anti-stress agent of great therapeutic relevance. This study indicates the beneficial role of Morus alba for the treatment of oxidative stress-induced disorders.

Effects of chronic restraint stress on social behaviors and the number of hypothalamic oxytocin neurons in male rats.

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Li, Jin; Li, Han-Xia; Shou, Xiao-Jing; Xu, Xin-Jie; Song, Tian-Jia; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2016-12-01

Oxytocin (OXT) and vasopressin (AVP) are considered to be related to mammalian social behavior and the regulation of stress responses. The present study investigated the effects of chronic homotypic restraint stress (CHRS) on social behaviors and anxiety, as well as its repercussions on OXT- and AVP-positive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) nuclei in rat. Male Sprague-Dawley rats receiving CHRS were exposed to repeated restraint stress of 30min per day for 10days. Changes in social approach behaviors were evaluated with the three-chambered social approach task. Changes in anxiety-like behaviors were evaluated in the light-dark box test. The number of neurons expressing oxytocin and/or vasopressin in PVN and SON were examined by immunohistochemistry techniques. The results demonstrated that social approach was increased and anxiety was decreased following 10-day exposure to CHRS. Furthermore, the number of OXT-immunoreactive cells in PVN was increased significantly, whereas no change in SON was seen. The number of AVP immunoreactive cells either in PVN or SON was unaffected. The results of this study suggest that certain types of stress could be effective in the treatment of social dysfunction in persons with mental disorders such as autism, social anxiety disorder. The therapeutic effects may be mediated by changes in the function of OXT neurons in PVN. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus.

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Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Zadeh, Sadaf Sarraf; Pour, Marieh Hossein; Ahmadiani, Abolhassan; Khodagholi, Fariba; Ashabi, Ghorbangol; Alamdary, Shabnam Zeighamy; Samami, Elham

2013-08-21

Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. It also reduced plasma corticosterone compared with the stressed animals. Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts. Copyright © 2013 Elsevier B.V. All rights reserved.

The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex

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M. M. Menezes

2013-01-01

Full Text Available Metabotropic glutamate 2/3 (mGlu2/3 receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL and infralimbic (IL cortex. LY354740 (10 and 30 mg/kg, i.p. showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.. Because both compounds inhibit serotonin 2A receptor (5-HT2AR-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

The interaction of chronic restraint stress and voluntary alcohol intake: effects on spatial memory in male rats.

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Gomez, Juan L; Lewis, Michael J; Luine, Victoria N

2012-08-01

Alcohol consumption and exposure to stressful life events activate similar neural pathways and thus result in several comparable physiological and behavioral effects. Alcoholics in treatment claim that life stressors are the leading cause of continued drinking or relapse. However, few studies have investigated the interactive effects of stress and alcohol on cognitive behavior. The effects of restraint stress, alcohol, and stress in combination with alcohol were examined on a spatial memory test, the object placement (OP) task. In addition, intake levels were measured to determine if stress altered general consumption of alcohol. Male Sprague-Dawley rats were assigned to one of four conditions: no alcohol/no stress control (CON), stress alone (STR), alcohol alone (ALC), and STR+alcohol (STR+ALC). Following each restraint stress bout, the STR+ALC and the ALC groups were given access to 8% alcohol for 1h using the two-bottle choice limited access paradigm. As predicted, the STR+ALC group significantly increased alcohol consumption, while the ALC group had consistent drinking over the 10-day treatment. On the OP task, STR and ALC groups performed at chance levels, whereas the CON and STR+ALC groups significantly discriminated between objects in the new and old locations. These data show that stress increases alcohol intake and the intake of alcohol is associated with reduction of the stress-induced impairment of spatial memory. The data have important implications for the development of alcohol abuse and its treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response.

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Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B; De Giovanni, Laura N; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E; Spear, Linda P; Pautassi, Ricardo Marcos

2016-03-01

Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

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Paré, W P; Burken, M I; Allen, E D; Kluczynski, J M

1993-01-01

Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

Possible Involvement of µ Opioid Receptor in the Antidepressant-Like Effect of Shuyu Formula in Restraint Stress-Induced Depression-Like Rats

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Fu-rong Wang

2015-01-01

Full Text Available Recently μ opioid receptor (MOR has been shown to be closely associated with depression. Here we investigated the action of Shuyu, a Chinese herbal prescription, on repeated restraint stress induced depression-like rats, with specific attention to the role of MOR and the related signal cascade. Our results showed that repeated restraint stress caused significant depressive-like behaviors, as evidenced by reduced body weight gain, prolonged duration of immobility in forced swimming test, and decreased number of square-crossings and rearings in open field test. The stress-induced depression-like behaviors were relieved by Shuyu, which was accompanied by decreased expression of MOR in hippocampus. Furthermore, Shuyu upregulated BDNF protein expression, restored the activity of CREB, and stimulated MEK and ERK phosphorylation in hippocampus of stressed rats. More importantly, MOR is involved in the effects of Shuyu on these depression-related signals, as they can be strengthened by MOR antagonist CTAP. Collectively, these data indicated that the antidepressant-like properties of Shuyu are associated with MOR and the corresponding CREB, BDNF, MEK, and ERK signal pathway. Our study supports clinical use of Shuyu as an effective treatment of depression and also suggests that MOR might be a target for treatment of depression and developing novel antidepressants.

Restraint stress intensifies interstitial K+ accumulation during severe hypoxia

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Christian eSchnell

2012-03-01

Full Text Available Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for three weeks (6 h/day. In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current (DC potential shift was shortened after stress. Moreover, K+ fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K+ levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for GFAP (glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K+ channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance and K+-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K+ accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K+ buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain.

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

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Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

2013-08-29

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

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Anna Rita Zuena

Full Text Available Prenatal Restraint Stress (PRS in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats" showed increased anxiety-like behavior in the elevated plus maze (EPM, a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.

Estrogen-dependent effects on behavior, lipid-profile, and glycemic index of ovariectomized rats subjected to chronic restraint stress.

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da Silva, Caroline Calice; Lazzaretti, Camilla; Fontanive, Tiago; Dartora, Daniela Ravizzoni; Bauereis, Brian; Gamaro, Giovana Duzzo

2014-03-01

Stress has been shown to negatively affect the immune system, alter the body's metabolism, and play a strong role in the development of mood disorders. These effects are mainly driven through the release of hormones from the hypothalamic-pituitary-adrenal axis (HPA). Additionally, women are more likely to be affected by stress due to the estrogen fluctuation associated with their menstrual cycle. This study aims to evaluate the effect of chronic restraint stress, applied for 30 days, and estrogen replacement on behavior, glucose level, and the lipid profile of ovariectomized rats. Our results suggest that stress increases sweet food consumption in OVX females treated with estradiol (E2), but reduces consumption in animals not treated. Furthermore, stress increases locomotor activity and anxiety as assessed by the Open Field test and in the Elevated Plus Maze. Similarly, our results suggest that E2 increases anxiety in female rats under the same behavioral tests. In addition, stress reduces glucose and TC levels. Moreover, stress increase TG levels in the presence of E2 and decrease in its absence, as well as the estradiol increase TG levels in stressed groups and reduced in non-stressed groups. Our data suggest an important interaction between stress and estrogen, showing that hormonal status can induce changes in the animal's response to stress. Copyright © 2014 Elsevier B.V. All rights reserved.

Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

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Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

2017-10-01

Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

Gestational or acute restraint in adulthood reduces levels of 5α-reduced testosterone metabolites in the hippocampus and produces behavioral inhibition of adult male rats

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Alicia A Walf

2012-12-01

Full Text Available Stressors, during early life or adulthood, can alter steroid-sensitive behaviors, such as exploration, anxiety, and/or cognitive processes. We investigated if exposure to acute stressors in adulthood may alter behavioral and neuroendocrine responses of male rats that were exposed to gestational stress or not. We hypothesized that rats exposed to gestational and acute stress may show behavioral inhibition, increased corticosterone, and altered androgen levels in the hippocampus. Subjects were adult, male offspring of rat dams that were restrained daily on gestational days 14-20, or did not experience this manipulation. Immediately before testing, rats were restraint-stressed for 20 minutes or not. During week 1, rats were tested in a battery of tasks, including the open field, elevated plus maze, social interaction, tailflick, pawlick, and defensive burying tasks. During week 2, rats were trained and tested 24 hours later in the inhibitory avoidance task. Plasma corticosterone and androgen levels, and hippocampal androgen levels, were measured in all subjects. Gestational and acute restraint stress increased plasma levels of corticosterone, and reduced levels of testosterone’s 5α-reduced metabolites, dihydrotestosterone and 3α-androstanediol, but not the aromatized metabolite, estradiol, in plasma or the hippocampus. Gestational and acute restraint stress reduced central entries made in the open field, and latencies to enter the shock-associated side of the inhibitory avoidance chamber during testing. Gestational stress reduced time spent interacting with a conspecific. These data suggest that gestational and acute restraint stress can have actions to produce behavioral inhibition coincident with increased corticosterone and decreased 5α-reduced androgens of adult male rats. Thus, gestational stress altered neural circuits involved in the neuroendocrine response to acute stress in early adulthood.

Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats.

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Hu, Wen; Zhang, Mingyue; Czéh, Boldizsár; Zhang, Weiqi; Flügge, Gabriele

2011-07-15

Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequences of these changes remained unclear. Here we demonstrate that chronic restraint stress causes a dysfunction in CB1 mediated modulation of GABAergic transmission in the hippocampus. Using an established protocol, adult male Sprague Dawley rats were daily restrained for 21 days and whole-cell voltage clamp was performed at CA1 pyramidal neurons. When recording carbachol-evoked inhibitory postsynaptic currents (IPSCs) which presumably originate from CB1 expressing cholecystokinin (CCK) interneurons, we found that depolarization-induced suppression of inhibition (DSI) was impaired by the stress. DSI is a form of short-term plasticity at GABAergic synapses that is known to be CB1 mediated and has been suggested to be involved in hippocampal information encoding. Chronic stress attenuated the depolarization-induced suppression of the frequency of carbachol-evoked IPSCs. Incubation with a CB1 receptor antagonist prevented this DSI effect in control but not in chronically stressed animals. The stress-induced impairment of CB1-mediated short-term plasticity at GABAergic synapses may underlie cognitive deficits which are commonly observed in animal models of stress as well as in patients with stress-related psychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

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Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

2015-06-01

Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

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Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

2015-04-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Intrauterine and lactation exposure to fluoxetine blunted in the offspring the aortic adaptive response induced by acute restraint stress.

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Marques, Bruno V D; Higashi, Carolina M; da S Novi, Daniella R B; Zanluqui, Nagela G; Gregório, Thais F; Pinge-Filho, Phileno; Gerardin, Daniela C C; Pelosi, Gislaine G; Moreira, Estefânia G; Ceravolo, Graziela S

2017-10-15

Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation. The experiments were performed in adult male offspring, treated or not with reserpine (4mg/Kg, ip, 28h before the experimental protocol). Fluoxetine and control rats were submitted to a single restraint stress session (ST) for 1h. Curves to phenylephrine were performed in thoracic aorta with endothelium. Aortic nitric oxide (NOx) were evaluated by the Griess method. The aortic contraction induced by phenylephrine was similar between control and fluoxetine rats. The acute stress reduced contraction in aorta of control ST compared to control, and L-NAME equaled this response. In fluoxetine rats, ST did not change the aortic constriction. Reserpine treatment restored the vasoconstriction in control ST, but did not interfere with aortic contraction in control, fluoxetine or fluoxetine ST. The NOx concentration was higher in aortas from control ST than control rats, and reserpine reduced NOx levels of control ST. The NOx concentration was similar between fluoxetine and fluoxetine ST rats, treated or not with reserpine. In conclusion, maternal treatment with fluoxetine blunted acute restraint stress-induced NO system activation and aortic adaptation in adult offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of MAPK and Dopaminergic Synapse Signaling Pathways in Antidepressant Effect of Electroacupuncture Pretreatment in Chronic Restraint Stress Rats

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Xinjing Yang

2017-01-01

Full Text Available Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20 and Yintang (GV29 was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

Cholinergic Modulation of Restraint Stress Induced Neurobehavioral ...

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The involvement of the cholinergic system in restraint stress induced neurobehavioral alterations was investigated in rodents using the hole board, elevated plus maze, the open field and the light and dark box tests. Restraint stress (3h) reduced significantly (p<0.05) the number of entries and time spent in the open arm, ...

Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism.

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Ball, Kevin T; Stone, Eric; Best, Olivia; Collins, Tyler; Edson, Hunter; Hagan, Erin; Nardini, Salvatore; Neuciler, Phelan; Smolinsky, Michael; Tosh, Lindsay; Woodlen, Kristin

2018-06-01

A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure. A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D 1 -like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement. Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D 1 -like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking. Copyright © 2018 Elsevier B.V. All rights reserved.

Methodological model of chronic stress associated with ligature-induced periodontitis in rats: a radiographic study

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Alex Semenoff Segundo

2010-12-01

Full Text Available This study evaluated the time efficiency of stress associated with ligature-induced periodontitis in rats. Sixty adult Wistar rats, housed in temperature-controlled rooms and receiving water and food ad libitum, were randomly separated into stress (n = 30 or control groups (n = 30. All animals were anesthetized, and nylon ligatures were placed at the gingival margin level of the maxillary right second molars. After the induction of periodontitis, rats in the stress group were subjected to physical restraint for 12 hours daily. The animals were euthanized after 7, 15 and 30 days by anesthetic overdose (10 animals per group per period. The right hemimaxillae were stored in formalin solution for 48 hours. Parallel radiographic images of the hemimaxillae were taken and processed following standard procedures. Radiographic examination was performed by a blinded and previously calibrated investigator. Bone height level was measured, and data were submitted to analysis of variance and post hoc Bonferroni tests (p 0.05. Restraint stress modulates the short-term progression of periodontal disease in rats. Therefore, the 12-hour daily physical restraint stress model in rats applied for up to 15 days is suitable for the investigation of the combined effect of ligation and restraint stress on periodontal degradation.

Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

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Moretto, Jillian N.; Duffy, Áine M.

2017-01-01

Although a great deal of information is available about the circuitry of the mossy cells (MCs) of the dentate gyrus (DG) hilus, their activity in vivo is not clear. The immediate early gene c-fos can be used to gain insight into the activity of MCs in vivo, because c-fos protein expression reflects increased neuronal activity. In prior work, it was identified that control rats that were perfusion-fixed after removal from their home cage exhibited c-fos immunoreactivity (ir) in the DG in a spatially stereotyped pattern: ventral MCs and dorsal granule cells (GCs) expressed c-fos protein (Duffy et al., Hippocampus 23:649–655, 2013). In this study, we hypothesized that restraint stress would alter c-fos-ir, because MCs express glucocorticoid type 2 receptors and the DG is considered to be involved in behaviors related to stress or anxiety. We show that acute restraint using a transparent nose cone for just 10 min led to reduced c-fos-ir in ventral MCs compared to control rats. In these comparisons, c-fos-ir was evaluated 30 min after the 10 min-long period of restraint, and if evaluation was later than 30 min c-fos-ir was no longer suppressed. Granule cells (GCs) also showed suppressed c-fos-ir after acute restraint, but it was different than MCs, because the suppression persisted for over 30 min after the restraint. We conclude that c-fos protein expression is rapidly and transiently reduced in ventral hilar MCs after a brief period of restraint, and suppressed longer in dorsal GCs. PMID:28190104

Effects of stress on gastrointestinal function: interactions of neural and endocrine systems in mediating stress-induced intestinal dysfunction in rats

International Nuclear Information System (INIS)

Williams, C.L.

1987-01-01

The etiology of stress-induced intestinal dysfunction is completely unresolved, and the lack of an appropriate animal model has hindered studies of causality. We compared a number of stressors and their resultant effects on intestinal transit, a measure of the propulsive motor activity of the gut, in the rat. We found that the response of the intestine to stress, and the neural systems activated by stress, were dependent on the type and duration of stress, as well as the animal strain, and gender. We developed a model, acute wrapping restraint stress, to fully characterize the effects of stress on intestinal transit. Wrap restraint stress is a nonulcerogenic model in which rats are subjected to acute restraint by wrapping them in a harness of paper tape to restrict, but not prevent movement of the upper body and forelimbs. Transit was evaluated by the geometric center method, in which a radiomarker ( 51 Cr) is instilled directly into the proximal duodenum and proximal colon via a surgically placed intestinal cannula, in fasted, adult female Sprague Dawley rats

Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors

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García-Iglesias, Brenda B.; Mendoza-Garrido, María E.; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A.

2013-01-01

Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex

Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

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Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

2016-02-01

Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

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Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

Interactive effects of chronic stress and a high-sucrose diet on nonalcoholic fatty liver in young adult male rats.

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Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Cuevas-Romero, Estela; Luna-Moreno, Dalia; Valente-Godínez, Héctor; Vázquez-Martínez, Olivia; Martínez-Gómez, Margarita; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

2017-11-01

Glucocorticoids have been implicated in nonalcoholic fatty liver diseases (NAFLD). The influence of a palatable diet on the response to stress is controversial. This study explored whether a high-sucrose diet could protect from hepatic steatosis induced by chronic restraint stress in young adult rats. Male Wistar rats aged 21 days were allocated into four groups (n = 6-8 per group): control, chronic restraint stress, 30% sucrose diet, and 30% sucrose diet plus chronic restraint stress. After being exposed to either tap water or sucrose solution during eight weeks, half of the rats belonging to each group were subject or not to repeated restraint stress (1 h per day, 5 days per week) during four weeks. Triacylglycerol (TAG), oxidative stress, activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), infiltration of immune cells, and glycogen amount in the liver were quantified. Serum concentrations of corticosterone and testosterone were also measured. The stressed group showed normal serum concentrations of corticosterone and did not have hepatic steatosis. However, this group showed increased glycogen, inflammation, mild fibrosis, oxidative stress, and a high activity of 11β-HSD-1 in the liver. The group exposed to the high-sucrose diet had lower concentrations of corticosterone, hepatic steatosis and moderate fibrosis. The group subject to high-sucrose diet plus chronic restraint stress showed low concentrations of corticosterone, hepatic steatosis, oxidative stress, and high concentrations of testosterone. Thus, restraint stress and a high-sucrose diet each generate different components of nonalcoholic fatty liver in young adult rats. The combination of both the factors could promote a faster development of NAFLD.

Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

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Douglas Carvalho Caixeta

Full Text Available Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats.

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Darya Tsvirkun

Full Text Available The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint, and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.

Effectiveness of somatodendritic and/or postsynaptic 5-ht-1A receptors following exposure to single restraint stress

International Nuclear Information System (INIS)

Samad, N.; Haleem, D.J.

2012-01-01

Effects of a selected dose of 8-hydroxy-2-(di-n-propylamino)tetralin (8-0H-DPAT) were studied on somatodendritic and/or postsynaptic S-hydroxytryptamine (S-HT; serotonin)-) A receptors responsiveness following exposure to single restraint stress. Rats were restrained for 2.h. 24-h after the termination of restraint period, 8-OH-DPAT at the doses of 0.25 mg/kg and saline (1 ml/kg), was injected to unrestrained and restrained animals. Activity in a light dark box was monitored. Intensity of 8-0H-DPAT-induced serotonin syndrome was monitored for 5-30 min post injection. Rats were decapitated I-h post-injection to collect brain samples for neurochemical estimation by high performance liquid chromatography with electrochemical detection (HPLC-EC). An episode of 2-h restraint stress decreased 24-h cumulative food intakes and changes in growth rates. Administration of 8-0H-DPAT increased time spent in light compartment in both unrestrained and restrained animals. Time spent in light compartment was smaller in 8-0H-DPAT injected restrained than unrestrained animals. Intensity of 8-0H-DPAT-induced serotonin syndrome monitored next day was smaller in restrained than unrestrained animals. Restrained animals injected with saline exhibited an increase in S-HT and S hydroxyindolacetic acid (S-HIAA) levels in the hippocampus, hypothalamus, midbrain and cortex but not in the striatum. 8-OH-DPAT decreased 5-HT and S-HIAA levels in different brain regions of unrestrained and restrained animals. The decreases were greater in restrained than unrestrained animals, suggesting a supersensitivity of somatodendritic S-HT -I A receptors. Stimulation of somatodendritic S-HT -I A receptor following exposure to an episode of 2-h restraint stress decreased the functional activity of postsynaptic S-HT -I A dependent responses. 8-OH-DP A T decreased S-HT and S-HIAA levels more in restrained than unrestrained animals, suggesting an increase in the effectiveness of somatodendritc 5-HT-IAA receptor

Acute Restraint Stress Alters Wheel-Running Behavior Immediately Following Stress and up to 20 Hours Later in House Mice.

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Malisch, Jessica L; deWolski, Karen; Meek, Thomas H; Acosta, Wendy; Middleton, Kevin M; Crino, Ondi L; Garland, Theodore

In vertebrates, acute stressors-although short in duration-can influence physiology and behavior over a longer time course, which might have important ramifications under natural conditions. In laboratory rats, for example, acute stress has been shown to increase anxiogenic behaviors for days after a stressor. In this study, we quantified voluntary wheel-running behavior for 22 h following a restraint stress and glucocorticoid levels 24 h postrestraint. We utilized mice from four replicate lines that have been selectively bred for high voluntary wheel-running activity (HR mice) for 60 generations and their nonselected control (C) lines to examine potential interactions between exercise propensity and sensitivity to stress. Following 6 d of wheel access on a 12L∶12D photo cycle (0700-1900 hours, as during the routine selective breeding protocol), 80 mice were physically restrained for 40 min, beginning at 1400 hours, while another 80 were left undisturbed. Relative to unrestrained mice, wheel running increased for both HR and C mice during the first hour postrestraint (P Wheel running was also examined at four distinct phases of the photoperiod. Running in the period of 1600-1840 hours was unaffected by restraint stress and did not differ statistically between HR and C mice. During the period of peak wheel running (1920-0140 hours), restrained mice tended to run fewer revolutions (-11%; two-tailed P = 0.0733), while HR mice ran 473% more than C (P = 0.0008), with no restraint × line type interaction. Wheel running declined for all mice in the latter part of the scotophase (0140-0600 hours), restraint had no statistical effect on wheel running, but HR again ran more than C (+467%; P = 0.0122). Finally, during the start of the photophase (0720-1200 hours), restraint increased running by an average of 53% (P = 0.0443) in both line types, but HR and C mice did not differ statistically. Mice from HR lines had statistically higher plasma corticosterone concentrations

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

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Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

2017-05-04

Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

Comparative study of c-Fos expression in rat dorsal vagal complex and nucleus ambiguus induced by different durations of restraint water-immersion stress.

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Zhang, Yu-Yu; Cao, Guo-Hong; Zhu, Wen-Xing; Cui, Xi-Yun; Ai, Hong-Bin

2009-06-30

Restraint water-immersion stress (RWIS) of rats induces vagally-mediated gastric dysfunction. The present work explored the effects of different durations of RWIS on neuronal activities of the dorsal vagal complex (DVC) and the nucleus ambiguous (NA) in rats. Male Wistar rats were exposed to RWIS for 0, 30, 60, 120, or 180 min. Then, a c-Fos immunoperoxidase technique was utilized to assess neuronal activation. Resumptively, c-Fos expression in DVC and NA peaked at 60 min of stress, subsequently decreased gradually with increasing durations of RWIS. Interestingly, the most intense c-Fos expression was observed in the dorsal motor nucleus of the vagus (DMV) during the stress, followed by NA, nucleus of solitary tract (NTS) and area postrema (AP). The peak of c-Fos expression in caudal DMV appeared at 120 min of the stress, slower than that in rostral and intermediate DMV. The c-Fos expression in intermediate and caudal NTS was significantly more intense than that in rostral NTS. These results indicate that the neuronal hyperactivity of DMV, NA, NTS and AP, the primary center that control gastric functions, especially DMV and NA, may play an important role in the disorders of gastric motility and secretion induced by RWIS.

Comparative proteomic analysis of rats subjected to water immersion and restraint stress as an insight into gastric ulcers.

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Zhou, Zheng-Rong; Huang, Pan; Song, Guang-Hao; Zhang, Zhuang; An, Ke; Lu, Han-Wen; Ju, Xiao-Li; Ding, Wei

2017-10-01

In the present study, comparative proteomic analysis was performed in rats subjected to water immersion‑restraint stress (WRS). A total of 26 proteins were differentially expressed and identified using matrix‑assisted laser desorption/ionization time of flight mass spectrometry. Among the 26 differentially expressed protein spots identified, 13 proteins were significantly upregulated under WRS, including pyruvate kinase and calreticulin, which may be closely associated with energy metabolism. In addition, 12 proteins were downregulated under WRS, including hemoglobin subunit β‑2 and keratin type II cytoskeletal 8, which may be important in protein metabolism and cell death. Gene Ontology analysis revealed the cellular distribution, molecular function and biological processes of the identified proteins. The mRNA levels of certain differentially expressed proteins were analyzed using fluorescence quantitative polymerase chain reaction analysis. The results of the present study aimed to offer insights into proteins, which are differentially expressed in gastric ulcers in stress, and provide theoretical evidence of a radical cure for gastric ulcers in humans.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

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Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury.

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Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A

2012-05-17

We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism.

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Ball, Kevin T; Best, Olivia; Luo, Jonathan; Miller, Leah R

2017-02-15

Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-h sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3h/day×1day or 10days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1day or 7days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7days, but not 1day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D 1 -like receptors during chronic stress may help to prevent future relapse in dieters. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

DEFF Research Database (Denmark)

Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

2008-01-01

The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

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Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

2004-04-01

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

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Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

2018-01-01

A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

Tests of the Aversive Summation Hypothesis in Rats: Effects of Restraint Stress on Consummatory Successive Negative Contrast and Extinction in the Barnes Maze

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Ortega, Leonardo A.; Prado-Rivera, Mayerli A.; Cardenas-Poveda, D. Carolina; McLinden, Kristina A.; Glueck, Amanda C.; Gutierrez, German; Lamprea, Marisol R.; Papini, Mauricio R.

2013-01-01

The present research explored the effects of restraint stress on two situations involving incentive downshift: consummatory successive negative contrast (cSNC) and extinction of escape behavior in the Barnes maze. First, Experiment 1 confirmed that the restraint stress procedure used in these experiments increased levels of circulating…

Psychological Stress, Cocaine and Natural Reward Each Induce Endoplasmic Reticulum Stress Genes in Rat Brain

OpenAIRE

Pavlovsky, Ashly A.; Boehning, Darren; Li, Dingge; Zhang, Yafang; Fan, Xiuzhen; Green, Thomas A.

2013-01-01

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors Activating Transcription Factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently it is unknown the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated. The current study examines transcriptional responses of key ER stress target genes subsequent to psychologi...

Restraint stress and social defeat: What they have in common.

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Motta, Simone Cristina; Canteras, Newton Sabino

2015-07-01

Bob Blanchard was a great inspiration for our studies on the neural basis of social defense. In the present study, we compared the hypothalamic pattern of activation between social defeat and restraint stress. As important stress situations, both defeated and immobilized animals displayed a substantial increase in Fos in the parvicellular part of the paraventricular nucleus,mostly in the region that contains the CRH neurons. In addition, socially defeated animals, but not restrained animals, recruited elements of the medial hypothalamic conspecific-responsive circuit, a region also engaged in other forms of social behavior. Of particular interest, both defeated and immobilized animals presented a robust increase in Fos expression in specific regions of the lateral hypothalamic area (i.e., juxtaparaventricular and juxtadorsomedial regions) likely to convey septo-hippocampal information encoding the environmental boundary restriction observed in both forms of stress, and in the dorsomedial part of the dorsal premammillary nucleus which seems to work as a key player for the expression of, at least, part of the behavioral responses during both restraint and social defeat. These results indicate interesting commonalities between social defeat and restraint stress, suggesting, for the first time, a septo-hippocampal–hypothalamic path likely to respond to the environmental boundary restriction that may act as common stressor component for both types of stress. Moreover, the comparison of the neural circuits mediating physical restraint and social defense revealed a possible path for encoding the entrapment component during social confrontation.

Stress-induced rise in serum anti-brain autoantibody levels in the rat.

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Andrejević, S; Bukilica, M; Dimitrijević, M; Laban, O; Radulovic, J; Kovacevic-Jovanovic, V; Stanojevic, S; Vasiljevic, T; Marković, B M

1997-02-01

Sera from Wistar rats subjected to different stress procedures were tested by ELISA for the presence of autoantibodies with specificity for neuron-specific enolase (NSE) and S100 protein that are preferentially localized in neurons and glia, respectively. Autoantibodies were present in sera of animals before exposure to stress, and raised with age. Anti-NSE and anti-S100 autoantibody levels were increased one day after termination of restraint (2 hours daily, 10 days) and electric tail shock (80 shocks daily, 19 days), and in fifth and tenth week of overcrowding stress. Differences between stressed and control animals were not present one month following restraint and electric tail shock and in twentieth week of overcrowding.

Interactive effects of dietary restraint and adiposity on stress-induced eating and the food choice of children.

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Roemmich, James N; Lambiase, Maya J; Lobarinas, Christina L; Balantekin, Katherine N

2011-12-01

The Individual Differences Model posits that individual differences in physiological and psychological factors explain eating behaviors in response to stress. The purpose was to determine the effects of individual differences in adiposity, dietary restraint and stress reactivity on children's energy intake and food choices. A total of 40 boys and girls, age 8-12 years, with wide ranges of dietary restraint, adiposity, and stress reactivity were measured for total energy intake and choice of energy dense 'comfort' and lower density 'healthy' foods following reading and speech stressor manipulations. When exploring the interaction of dietary restraint and stress reactivity, lower restraint/lower reactivity and lower restraint/higher reactivity were associated with reductions in energy intake (37-62 kcal) and comfort food (33-89 kcal). Higher restraint/lower reactivity was associated with consuming 86 fewer total kcal and 45 fewer kcal of comfort food. Only higher restraint/higher reactivity predicted increased energy intake (104 kcal) and comfort food (131 kcal). The interaction of dietary restraint and percentage body fat revealed that lower restraint/lower adiposity was associated with consuming 123 fewer kcal after being stressed with the entire reduction due to a decrease in comfort food. Lower restraint/higher adiposity was associated with consuming 116 kcal more after being stressed with 70% (81 kcal) of the increase in the form of comfort foods. Higher restraint/lower adiposity and higher restraint/higher adiposity were associated with smaller changes in total energy intake of 22 kcal and 1 kcal; respectively. Both restraint and adiposity moderated the effect of stress on energy intake and food choice. Children with greater adiposity may be at risk for stress-induced eating to contribute to their obesity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

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Torres I.L.S.

2001-01-01

Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

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Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

2015-01-01

Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

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Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

2014-12-30

Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

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Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-09-01

Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol

Effects of Ginsenoside Rg1 on Learning and Memory in a Reward-directed Instrumental Conditioning Task in Chronic Restraint Stressed Rats.

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Kezhu, Wang; Pan, Xu; Cong, Lu; Liming, Dong; Beiyue, Zhang; Jingwei, Lu; Yanyan, Yang; Xinmin, Liu

2017-01-01

Ginsenoside Rg1 is one of the major active ingredients of Panax ginseng and has showed notable improving learning and memory effects in several behavioral tasks, such as water maze, shuttle-box, and step-through, based on avoidance. However, there was no report about the role of Rg1 on the performance of reward-directed instrumental conditioning, which could reflect the adaptive capacity to ever-changing environments. Thus, in this study, the reward devaluation test and conditional visual discrimination task were conducted to study the ameliorating effects of Rg1 on cognitive deficits, especially the loss of adaptation capacity in chronic restraint stress (CRS) rat model. Our results showed that rat subjected to CRS became insensitive to the changes in outcome value, and it significantly harmed the rat's performance in conditional visual discrimination task. Moreover, the levels of BDNF, TrkB, and Erk phosphorylation were decreased in the prefrontal cortex of CRS rats. However, these changes were effectively reversed by Rg1 (5 and 10 mg/kg, i.p.). Therefore, it demonstrated that Rg1 has a good ability to improve learning and memory and also ameliorate impaired adaptive capacity induced by CRS. This amelioration effect of Rg1 might be mediated partially by BDNF/TrkB/Erk pathway in prefrontal cortex. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

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Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2011-01-01

Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

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Popović Nataša

2010-01-01

Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model.

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Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Ahn, Yo-Chan; Son, Chang-Gue

2017-07-31

The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Chronic restraint stress after injury and shock is associated with persistent anemia despite prolonged elevation in erythropoietin levels.

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Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-07-01

Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (chronic stress [CS]) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia and prolong the initial anemia, despite elevated erythropoietin (EPO) levels. Male Sprague-Dawley rats (n = 6-8 per group) underwent lung contusion (LC) or combined LC/hemorrhagic shock (LCHS) followed by 6 days of CS. CS consisted of a 2-hour restraint period interrupted with repositioning and alarms every 30 minutes. At 7 days, urine was assessed for norepinephrine (NE) levels, blood for EPO and hemoglobin (Hgb), and BM for erythroid progenitor growth. Animals undergoing LC or combined LCHS predictably recovered by Day 7; urine NE, EPO, and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on Day 6. The addition of CS to LC led to a persistent 20% to 25% decrease in the growth of BM hematopoietic progenitor cells. These findings were further exaggerated when CS was added following LCHS, resulting in a 20%q to 40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared with LCHS alone. Exposing injured animals to CS results in prolonged elevation of NE and EPO, which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating CS after severe injury is a potential therapeutic target to improve BM dysfunction and anemia.

Increases in anxiety-like behavior induced by acute stress are reversed by ethanol in adolescent but not adult rats.

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Varlinskaya, Elena I; Spear, Linda P

2012-01-01

Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. Copyright © 2011 Elsevier Inc. All rights reserved.

Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

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María Eugenia Hernandez

2013-01-01

Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

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Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

2015-01-01

Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress analysis of two-dimensional C/C composite components for HTGR's core restraint techanism

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Satoshi Hanawa; Taiju Shibata; Jyunya Sumita; Masahiro Ishihara; Tatsuo Iyoku; Kazuhiro Sawa

2005-01-01

Carbon fiber reinforced carbon matrix composite (C/C composite) is one of the most promising materials for HTGRs core components due to their high strength as well as high temperature resistibility. One of the most attractive applications of C/C composite is the core restraint mechanism. The core restraint mechanism is located around the reflector block and it works to tighten reactor core blocks so as to restrict un-supposition flow pass of coolant gas (bypass flow) in the core. The restriction of bypass flow reads to the high efficiency of coolant flow rate inside of the reactor core. For the future HTGRs and VHTR (Very High Temperature Reactor), it is important to develop the core restraint mechanism with C/C composite substitute for metallic materials as used for HTTR. For the application of C/C composite to core restraint mechanism, it is important to investigate the applicability of C/C composite in viewpoint of structural integrity. In the present study, supposing the application of 2D-C/C composite to core restraint mechanism, thermal stress behavior was analyzed by considering the thickness of the C/C composite and the gap between reflector block and core restraint. It was shown from the thermal stress analysis that the circumferential stress decreases with increasing the gap and that the restraint force increases with increasing the thickness. By optimizing the thickness of C/C composite and gap between reflector block and core restraint, the C/C composite is applicable to the core restraint mechanism. (authors)

Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice.

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Jeong, Joo Yeon; Lee, Dong Hoon; Kang, Sang Soo

2013-12-01

Stress affects body weight and food intake, but the underlying mechanisms are not well understood. We evaluated the changes in body weight and food intake of ICR male mice subjected to daily 2 hours restraint stress for 15 days. Hypothalamic gene expression profiling was analyzed by cDNA microarray. Daily body weight and food intake measurements revealed that both parameters decreased rapidly after initiating daily restraint stress. Body weights of stressed mice then remained significantly lower than the control body weights, even though food intake slowly recovered to 90% of the control intake at the end of the experiment. cDNA microarray analysis revealed that chronic restraint stress affects the expression of hypothalamic genes possibly related to body weight control. Since decreases of daily food intake and body weight were remarkable in days 1 to 4 of restraint, we examined the expression of food intake-related genes in the hypothalamus. During these periods, the expressions of ghrelin and pro-opiomelanocortin mRNA were significantly changed in mice undergoing restraint stress. Moreover, daily serum corticosterone levels gradually increased, while leptin levels significantly decreased. The present study demonstrates that restraint stress affects body weight and food intake by initially modifying canonical food intake-related genes and then later modifying other genes involved in energy metabolism. These genetic changes appear to be mediated, at least in part, by corticosterone.

Estrogen and voluntary exercise interact to attenuate stress-induced corticosterone release but not anxiety-like behaviors in female rats.

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Jones, Alexis B; Gupton, Rebecca; Curtis, Kathleen S

2016-09-15

The beneficial effects of physical exercise to reduce anxiety and depression and to alleviate stress are increasingly supported in research studies. The role of ovarian hormones in interactions between exercise and anxiety/stress has important implications for women's health, given that women are at increased risk of developing anxiety-related disorders, particularly during and after the menopausal transition. In these experiments, we tested the hypothesis that estrogen enhances the positive impact of exercise on stress responses by investigating the combined effects of exercise and estrogen on anxiety-like behaviors and stress hormone levels in female rats after an acute stressor. Ovariectomized female rats with or without estrogen were given access to running wheels for one or three days of voluntary running immediately after or two days prior to being subjected to restraint stress. We found that voluntary running was not effective at reducing anxiety-like behaviors, whether or not rats were subjected to restraint stress. In contrast, stress-induced elevations of stress hormone levels were attenuated by exercise experience in estrogen-treated rats, but were increased in rats without estrogen. These results suggest that voluntary exercise may be more effective at reducing stress hormone levels if estrogen is present. Additionally, exercise experience, or the distance run, may be important in reducing stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

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Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

2016-01-01

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

The antioxidant effects of dry apricot in the various tissues of rats with induced cold restraint stress.

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Uguralp, S; Ozturk, F; Aktay, G; Cetin, A; Gursoy, S

2012-01-01

α-Tocopherol and β-carotene are the best known and most widely used natural antioxidant substances. Apricot contains β-carotene, tocopherols and flavonoids. This experimental study was designed to investigate the protective effect of Malatya kabashi apricot in stress-induced injury in various tissues of rats. In total, 32 male Wistar albino rats were divided into four groups: control, apricot, stress and apricot-stress groups. Apricot was administrated to rats by gavage for 10 days in the apricot and apricot-stress groups. Then rats were kept at 4°C for 4 h in stress and apricot-stress groups. The rats were killed at the end of the experiment for biochemical and histological examinations. This study shows apricot supplementation decreased oxidative stress injury in both the stomach and intestine.

Granule cell potentials in the dentate gyrus of the hippocampus: coping behavior and stress ulcers in rats.

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Henke, P G

1990-01-01

Evoked population potentials of the granule cells in the dentate gyrus of the hippocampus were increased in stress-resistant rats and decreased in stress-susceptible rats, as indexed by restraint-induced gastric ulcers. Inescapable, uncontrollable shock stimulation also suppressed granule cell population spikes and interfered with subsequent coping responses when escape was possible, i.e. the so-called helplessness effect. The data were interpreted to indicate that the hippocampus is part of a coping system in stressful situations.

Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.

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Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C

2014-01-01

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

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Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

2015-01-01

Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

How Farm Animals React and Perceive Stressful Situations Such As Handling, Restraint, and Transport

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Temple Grandin

2015-12-01

Full Text Available An animal that has been carefully acclimated to handling may willingly re-enter a restrainer. Another animal may have an intense agitated behavioral reaction or refuse to re-enter the handling facility. Physiological measures of stress such as cortisol may be very low in the animal that re-enters willingly and higher in animals that actively resist restraint. Carefully acclimating young animals to handling and restraint can help improve both productivity and welfare by reducing fear stress. Some of the topics covered in this review are: How an animal perceives handling and restraint, the detrimental effects of a sudden novel event, descriptions of temperament and aversion tests and the importance of good stockmanship.

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro

NARCIS (Netherlands)

Bijlsma, P. B.; van Raaij, M. T.; Dobbe, C. J.; Timmerman, A.; Kiliaan, A. J.; Taminiau, J. A.; Groot, J. A.

2001-01-01

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to

Regulation of body temperature and nociception induced by non-noxious stress in rat.

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Vidal, C; Suaudeau, C; Jacob, J

1984-04-09

The effects of 3 different non-noxious stressors on body temperature (Tb) were investigated in the rat: (1) loose restraint in cylinders, (2) removal of the rats from cylinders, exposure to a novel environment and replacement in cylinders, a stressor called here 'novelty', and (3) gentle holding of the rats by the nape of the neck. Loose restraint and 'novelty' produced hyperthermia. On the contrary, holding induced hypothermia. Hypophysectomy (HX) reduced basal Tb, abolished restraint hyperthermia and reduced both 'novelty' hyperthermia and holding hypothermia. Dexamethasone ( DEXA ) had no effect upon either restraint or novelty hyperthermia but reduced the hypothermia. Naloxone (Nx) produced a slight fall in basal Tb accounting for its reduction of restraint and 'novelty' hyperthermias ; it did not affect holding hypothermia. The inhibitory effects of HX suggest a participation of the pituitary in the hyperthermias ; the neurointermediate lobe would be involved as the hyperthermias were not affected by DEXA , which is known to block the stress-induced release of pituitary secretions from the anterior lobe but not from the neurointermediate lobe. In contrast, substances from the anterior lobe might participate in hypothermia due to holding since it is reduced by HX and DEXA . As to the effects of Nx, endogenous opioids would not be significantly involved in the thermic effects of the stressors used in this study; they might play, if any, only a minor role in the regulation of basal Tb. These results are compared with those previously obtained on nociception using the same non-noxious stressors. It emerges that, depending on the stressor, different types of association between thermoregulation and nociception may occur, i.e. hyperthermia with analgesia, hyperthermia with hyperalgesia and hypothermia with hyperalgesia.

c-Fos expression in the supraoptic nucleus is the most intense during different durations of restraint water-immersion stress in the rat.

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Zhang, Yu-Yu; Zhu, Wen-Xing; Cao, Guo-Hong; Cui, Xi-Yun; Ai, Hong-Bin

2009-09-01

Restraint water-immersion stress (RWIS) can induce anxiety, hypothermia, and severe vagally-mediated gastric dysfunction. The present work explored the effects of different durations of RWIS on neuronal activities of the forebrain by c-Fos expression in conscious rats exposed to RWIS for 0, 30, 60, 120, or 180 min. The peak of c-Fos induction was distinct for different forebrain regions. The most intense c-Fos induction was always observed in the supraoptic nucleus (SON), and then in the hypothalamic paraventricular nucleus (PVN), posterior cortical amygdaloid nucleus (PCoA), central amygdaloid nucleus (CeA), and medial prefrontal cortex (mPFC). Moreover, body temperature was reduced to the lowest degree after 60 min of RWIS, and the gastric lesions tended to gradually worsen with the prolonging of RWIS duration. These data strongly suggest that these nuclei participate in the organismal response to RWIS to different degrees, and may be involved in the hypothermia and gastric lesions induced by RWIS.

Orexins Mediate Sex Differences in the Stress Response and in Cognitive Flexibility.

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Grafe, Laura A; Cornfeld, Amanda; Luz, Sandra; Valentino, Rita; Bhatnagar, Seema

2017-04-15

Women are twice as likely as men to experience stress-related psychiatric disorders. The biological basis of these sex differences is poorly understood. Orexins are altered in anxious and depressed patients. Using a rat model of repeated stress, we examined whether orexins contribute to sex differences in outcomes relevant to stress-related psychiatric diseases. Behavioral, neural, and endocrine habituation to repeated restraint stress and subsequent cognitive flexibility was examined in adult male and female rats. In parallel, orexin expression and activation were determined in both sexes, and chromatin immunoprecipitation was used to determine transcription factors acting at the orexin promoter. Designer receptors exclusively activated by designer drugs were used to inhibit orexin activation throughout repeated restraint to determine if the stress-related impairments in female rats could be reduced. Female rats exhibited impaired habituation to repeated restraint with subsequent deficits in cognitive flexibility compared with male rats. Increased orexin expression and activation were observed in female rats compared with male rats. The higher expression of orexin messenger RNA in female rats was due to actions of glucocorticoid receptors on the orexin promoter, as determined by chromatin immunoprecipitation. Inhibition of orexins using designer receptors exclusively activated by designer drugs in female rats throughout repeated restraint abolished their heightened hypothalamic-pituitary-adrenal responsivity and reduced stress-induced cognitive impairments. Orexins mediate the impairments in adaptations to repeated stress and in subsequent cognitive flexibility exhibited by female rats and provide evidence for a broader role for orexins in mediating functions relevant to stress-related psychiatric diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice.

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Priscila Marianno

Full Text Available Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h or continuous (24 h EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase. Control mice were housed under standard conditions (SC. In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h. In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h. After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.

Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

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Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-04-01

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

Social factors modulate restraint stress induced hyperthermia in mice.

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Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Restraint stress in lactating mice alters the levels of sulfur-containing amino acids in milk.

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Nishigawa, Takuma; Nagamachi, Satsuki; Ikeda, Hiromi; Chowdhury, Vishwajit S; Furuse, Mitsuhiro

2018-03-30

It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring's body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

[Effects of psychological stress on performances in open-field test of rats and tyrosine's modulation].

Science.gov (United States)

Chen, Wei-Qiang; Cheng, Yi-Yong; Li, Shu-Tian; Hong, Yan; Wang, Dong-Lan; Hou, Yue

2009-02-01

To explore the effects of different doses of tyrosine modulation on behavioral performances in open field test of psychological stress rats. The animal model of psychological stress was developed by restraint stress for 21 days. Wistar rats were randomly assigned to five groups (n = 10) as follows: control group (CT), stress control group (SCT), low, medium and high-doses of tyrosine modulation stress groups (SLT, SMT and SIT). The changes of behavioral performances were examined by open-field test. Serum levels of cortisol, norepinephrine and dopamine were also detected. The levels of serum cortisol were all increased obviously in the four stress groups, and their bodyweight gainings were diminished. The behavioral performances of SCT rats in open-field test were changed significantly in contrast to that of CT rats. However, The behavioral performances of SMT and SHT rats were not different from that of CT rats. In addition, the serum levels of norepinephrine and dopamine were downregulated obviously in SCT and SLT groups, and no differences were observed in other groups. Psychological stress can impair body behavioral performances, and moderate tyrosine modulation may improve these abnormal changes. The related mechanisms may be involved with the changes of norepinephrine and dopamine.

Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

DEFF Research Database (Denmark)

Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.

2011-01-01

An increasing number of scientific studies indicate that maternal stress during pregnancy influences fetal development of the nervous system and thereby the behavioural phenotype. We have previously reported attenuated prepulse inhibition (PPI) of the startle reaction in adult female rats derived...... paradigm of stressors affected the PPI response pattern in male rats. In prenatally manipulated males, the PPI response differed statistically significantly, depending on prior exposure to an episode of postnatal acute stress (blood sampling under restraint). In contrast, the PPI response in control males...... was unaffected by this postnatal experience. The present work supports the hypothesis that the maternal environment is a long-term determinant of phenotypic differences in sensitivity to stressors....

Assessing competence of broccoli consumption on inflammatory and antioxidant pathways in restraint-induced models: estimation in rat hippocampus and prefrontal cortex.

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Khalaj, Leila; Nejad, Sara Chavoshi; Mohammadi, Marzieh; Sarraf Zadeh, Sadaf; Pour, Marieh Hossein; Ashabi, Ghorbangol; Khodagholi, Fariba; Ahmadiani, Abolhassan

2013-01-01

A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA) level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

Assessing Competence of Broccoli Consumption on Inflammatory and Antioxidant Pathways in Restraint-Induced Models: Estimation in Rat Hippocampus and Prefrontal Cortex

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Leila Khalaj

2013-01-01

Full Text Available A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2 antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

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Jiang, Sunny Zhihong; Eiden, Lee E

2016-07-01

We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

Adrenal-dependent and -independent stress-induced Per1 mRNA in hypothalamic paraventricular nucleus and prefrontal cortex of male and female rats.

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Chun, Lauren E; Christensen, Jenny; Woodruff, Elizabeth R; Morton, Sarah J; Hinds, Laura R; Spencer, Robert L

2018-01-01

Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extra-SCN brain regions. These extra-SCN molecular clocks depend on the SCN for entrainment to a light:dark cycle. The SCN has limited neural efferents, so it may entrain extra-SCN molecular clocks through its well-established circadian control of glucocorticoid hormone secretion. Glucocorticoids can regulate the normal rhythmic expression of clock genes in some extra-SCN tissues. Untimely stress-induced glucocorticoid secretion may compromise extra-SCN molecular clock function. We examined whether acute restraint stress during the rat's inactive phase can rapidly (within 30 min) alter clock gene (Per1, Per2, Bmal1) and cFos mRNA (in situ hybridization) in the SCN, hypothalamic paraventricular nucleus (PVN), and prefrontal cortex (PFC) of male and female rats (6 rats per treatment group). Restraint stress increased Per1 and cFos mRNA in the PVN and PFC of both sexes. Stress also increased cFos mRNA in the SCN of male rats, but not when subsequently tested during their active phase. We also examined in male rats whether endogenous glucocorticoids are necessary for stress-induced Per1 mRNA (6-7 rats per treatment group). Adrenalectomy attenuated stress-induced Per1 mRNA in the PVN and ventral orbital cortex, but not in the medial PFC. These data indicate that increased Per1 mRNA may be a means by which extra-SCN molecular clocks adapt to environmental stimuli (e.g. stress), and in the PFC this effect is largely independent of glucocorticoids.

Adrenocortical and behavioural response to chronic restraint stress in neurokinin-1 receptor knockout mice.

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Delgado-Morales, Raúl; del Río, Eva; Gómez-Román, Almudena; Bisagno, Verónica; Nadal, Roser; de Felipe, Carmen; Armario, Antonio

2012-02-01

Brain substance P and its receptor (neurokinin-1, NK1) have a widespread brain distribution and are involved in an important number of behavioural and physiological responses to emotional stimuli. However, the role of NK1 receptors in the consequences of exposure to chronic stress has not been explored. The present study focused on the role of these receptors in the hypothalamic-pituitary-adrenal (HPA) response to daily repeated restraint stress (evaluated by plasma corticosterone levels), as well as on the effect of this procedure on anxiety-like behaviour, spatial learning and memory in the Morris water maze (MWM), a hippocampus-dependent task. Adult null mutant NK1-/- mice, with a C57BL/6J background, and the corresponding wild-type mice showed similar resting corticosterone levels and, also, did not differ in corticosterone response to a first restraint. Nevertheless, adaptation to the repeated stressor was faster in NK1-/- mice. Chronic restraint modestly increased anxiety-like behaviour in the light-dark test, irrespective of genotype. Throughout the days of the MWM trials, NK1-/- mice showed a similar learning rate to that of wild-type mice, but had lower levels of thigmotaxis and showed a better retention in the probe trial. Chronic restraint stress did not affect these variables in either genotype. These results indicate that deletion of the NK1 receptor does not alter behavioural susceptibility to chronic repeated stress in mice, but accelerates adaptation of the HPA axis. In addition, deletion may result in lower levels of thigmotaxis and improved short-term spatial memory, perhaps reflecting a better learning strategy in the MWM. Copyright © 2011 Elsevier Inc. All rights reserved.

Behavioral and Neurochemical Studies in Stressed and Unstressed Rats Fed on Protein, Carbohydrate and Fat Rich Diet

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Samia Moin§, Saida Haider*, Saima Khaliq1, Saiqa Tabassum and Darakhshan J. Haleem

2012-05-01

Full Text Available Stress produces behavioral and neurochemical deficits. To study the relationship between adaptation to stress and macronutrient intake, the present study was designed to monitor the effects of different diets on feed intake, growth rate and serotonin (5-Hydroxytryptamine, 5-HT metabolism following exposure to restraint stress in rats. Rats were divided into four groups (n=12 as control, sugar, protein and fat rich diet fed rats. After 5 weeks of treatment animals of each group were divided into unrestrained and restrained animals (n=6. Rats of restrained group were given immobilization stress for 2 hours/day for 5 days. Food intake and growth rates of unrestrained and restrained rats were monitored daily. Rats were decapitated on 6th day to collect brain samples for neurochemical estimation. Results show that sugar diet fed rats produced adaptation to stress early as compared to normal diet fed rats. Food intake and growth rates of unrestrained and restrained rats were comparable on 3rd day in sugar diet fed rats and on 4th day in normal diet fed rats. Stress decreased food intake and growth rates of protein and fat treated rats. Repeated stress did not alter brain 5-HT and 5-HIAA levels of normal diet fed rats and sugar diet fed rats. Protein diet fed restrained rats showed elevated brain 5-HT levels. Fat diet fed restrained rats significantly decreased brain TRP and 5-HIAA levels. Finding suggested that carbohydrate diet might protect against stressful conditions. Study also showed that nutritional status could alter different behaviors in response to a stressful environment.

Repeated Neck Restraint Stress Bidirectionally Modulates Excitatory Transmission in the Dentate Gyrus and Performance in a Hippocampus-dependent Memory Task.

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Spyrka, Jadwiga; Hess, Grzegorz

2018-05-21

The consequences of stress depend on characteristics of the stressor, including the duration of exposure, severity, and predictability. Exposure of mice to repeated neck restraint has been shown to bidirectionally modulate the potential for long-term potentiation (LTP) in the dentate gyrus (DG) in a manner dependent on the number of restraint repetitions, but the influence of repeated brief neck restraint on electrophysiology of single DG neurons has not yet been investigated. Here, we aimed at finding the effects of 1, 3, 7, 14, or 21 daily neck restraint sessions lasting 10 min on electrophysiological characteristics of DG granule cells as well as excitatory and inhibitory synaptic inputs to these neurons. While the excitability of DG granule cells and inhibitory synaptic transmission were unchanged, neck restraint decreased the frequency of spontaneous excitatory currents after three repetitions but enhanced it after 14 and 21 repetitions. The consequences of repeated neck restraint on hippocampus-dependent memory were investigated using the object location test (OLT). Neck restraint stress impaired cognitive performance in the OLT after three repetitions but improved it after 14 and 21 repetitions. Mice subjected to three neck restraint sessions displayed an increase in the measures of depressive and anxiety-like behaviors, however, prolongation of the exposure to neck restraint resulted in a gradual decline in the intensity of these measures. These data indicate that stress imposed by an increasing number of repeated neck restraint episodes bidirectionally modulates both excitatory synaptic transmission in the DG and cognitive performance in the object location memory task. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of fish oil and coconut fat supplementation on depressive-type behavior and corticosterone levels of prenatally stressed male rats.

Science.gov (United States)

Borsonelo, Elizabethe Cristina; Suchecki, Deborah; Galduróz, José Carlos Fernandes

2011-04-18

Prenatal stress (PNS) during critical periods of brain development has been associated with numerous behavioral and/or mood disorders in later life. These outcomes may result from changes in the hypothalamic-pituitary-adrenal (HPA) axis activity, which, in turn, can be modulated by environmental factors, such as nutritional status. In this study, the adult male offspring of dams exposed to restraint stress during the last semester of pregnancy and fed different diets were evaluated for depressive-like behavior in the forced swimming test and for the corticosterone response to the test. Female Wistar rats were allocated to one of three groups: regular diet, diet supplemented with coconut fat or with fish oil, offered during pregnancy and lactation. When pregnancy was confirmed, they were distributed into control or stress groups. Stress consisted of restraint and bright light for 45 min, three times per day, in the last week of pregnancy. The body weight of the adult offspring submitted to PNS was lower than that of controls. In the forced swimming test, time of immobility was reduced and swimming was increased in PNS rats fed fish oil and plasma corticosterone levels immediately after the forced swimming test were lower in PNS rats fed regular diet than their control counterparts; this response was reduced in control rats whose mothers were fed fish oil and coconut fat. The present results indicate that coconut fat and fish oil influenced behavioral and hormonal responses to the forced swimming test in both control and PNS adult male rats. Copyright © 2011 Elsevier B.V. All rights reserved.

Variety of immune responses to chronic stress in rats male

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Іlona S Polovynko

2016-12-01

Full Text Available Background. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress in male rats. Revealed that the value of canonical discriminant roots rats subjected to chronic stress different not only on the values of intact animals (by definition, but also among themselves. So we set a goal retrospectively divided stressed rats into three homogeneous groups. Material and methods. The experiment is at 50 white male rats. Of these 10 animals not subjected to any influences and 40 within 7 days subjected to moderate stress by daily 30-minute immobilization. The day after the completion of stressing in portion of the blood immunological parameters were determined by tests I and II levels of WHO. The spleen and thymus did smears for counting spleno- and thymocytograms. Results. The method of cluster analysis (k-means clustering formed three groups-clusters. For further analysis selected 18 parameters that members of each cluster differing minimum and maximum are different from members of other clusters (η2=0,73÷0,15; F=49,0÷3,26; p=10-6÷0,05. We stated that in 16 rats from cluster III the deviation 16 parameters in either side of the average norm almost identical and are in an acceptable range of ±0,5σ. Thus, the immune status of 40% of the rats subjected to moderate chronic stress was resistant to its factors. For the immune status of the 15 (37,5% rats cluster II typical moderate inhibition microphage, killer and T-cellular links in combination with a strong activation macrophage link. Poststressory changes in immunity in 9 rats (22,5% from cluster I differ from those in cluster II both qualitatively and quantitatively. In particular, the rats in this cluster were found no deviations from the norm or reaction blast transformation T-cells nor NK-lymphocytes levels. However, other parameters of T-link and microhage link suppressed more and settings macrophage link appeared

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

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Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

2016-05-04

DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

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Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

2016-10-15

The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright �

Chronic stress effects and their reversibility on the Fallopian tubes and uterus in rats.

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Divyashree, S; Yajurvedi, H N

2018-01-01

The durational effects of chronic stress on the Fallopian tubes and uterus were studied by exposing rats to stressors in the form of restraint (1h) and forced swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each time period was then maintained without exposure to stressors for a further 4 weeks to assess their ability to recover from stress. All time periods of stress exposure resulted in decreased weight of the body and Fallopian tubes; however, the relative weight of the uterus and serum concentrations of oestradiol and insulin increased significantly. The antioxidant potential was decreased with increased malondialdehyde concentrations in the Fallopian tubes following all durations of exposure and after 4 and 8 weeks of stress exposure in the uterus. Interestingly, rats stressed for 12 weeks showed an increase in serum testosterone concentration and antioxidant enzyme activities with a decrease in malondialdehyde concentration in the uterus. The antioxidant enzyme activities and malondialdehyde concentration in the Fallopian tubes of all recovery group rats were similar to stressed rats. However, in the uterus these parameters were similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure, but after 12 weeks of stress exposure these parameters did not return to control levels following the recovery period. These results reveal, for the first time, that chronic stress elicits an irreversible decrease in antioxidant defence in the Fallopian tubes irrespective of exposure duration, whereas the uterus develops reversible oxidative stress under short-term exposure but increased antioxidant potential with endometrial proliferation following long-term exposure.

Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: Role of antioxidant enzymes.

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Emad, Shaista; Qadeer, Sara; Sadaf, Sana; Batool, Zehra; Haider, Saida; Perveen, Tahira

2017-04-01

Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antioxidant enzymes along with the activity of acetylcholinesterase (AChE). Results of MWM and EPM showed significant effects of drugs in both unrestraint and restraint rats as escape latency and transfer latency, in respective behavioral models were decreased as compared to that of control. This study also showed NSAIDs administration decreased LPO and increased antioxidant enzymes activity and decreased AChE activity in rats exposed to repeated stress. In conclusion this study suggests a therapeutic potential of indomethacin and diclofenac against repeated stress-induced memory deficits. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats

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Therese A. Kosten

2012-03-01

Full Text Available Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA axis activity. Yet, compared to Fischer 344 (F344 rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg from saline using a two-lever, food-reinforced (FR10 procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

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Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

2006-12-01

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Behavioral effects of acclimatization to restraint protocol used for awake animal imaging.

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Reed, Michael D; Pira, Ashley S; Febo, Marcelo

2013-07-15

Functional MRI in awake rats involves acclimatization to restraint to minimize motion. We designed a study to examine the effects of an acclimatization protocol (5 days of restraint, 60 min per day) on the emission of 22-kHz ultrasonic vocalizations and performance in a forced swim test (FST). Our results showed that USV calls are reduced significantly by days 3, 4 and 5 of acclimatization. Although the rats showed less climbing activity (and more immobility) in FST on day 5 compared to the 1st day of restraint acclimatization, the difference was not detected once the animals were given a 2-week hiatus. Overall, we showed that animals adapt to the restraint over a five-day period; however, restraint may introduce confounding behavioral outcomes that may hinder the interpretation of results derived from awake rat imaging. The present data warrants further testing of the effects of MRI restraint on behavior. Copyright © 2013 Elsevier B.V. All rights reserved.

Chronic restraint stress induces sperm acrosome reaction and changes in testicular tyrosine phosphorylated proteins in rats

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Supatcharee Arun

2016-07-01

Full Text Available Background: Stress is a cause of male infertility. Although sex hormones and sperm quality have been shown to be low in stress, sperm physiology and testicular functional proteins, such as phosphotyrosine proteins, have not been documented. Objective: To investigate the acrosome status and alterations of testicular proteins involved in spermatogenesis and testosterone synthesis in chronic stress in rats. Materials and Methods: In this experimental study, male rats were divided into 2 groups (control and chronic stress (CS, n=7. CS rats were immobilized (4 hr/day for 42 consecutive days. The blood glucose level (BGL, corticosterone, testosterone, acrosome status, and histopathology were examined. The expressions of testicular steroidogenic acute regulatory (StAR, cytochrome P450 side chain cleavage (CYP11A1, and phosphorylated proteins were analyzed. Results: Results showed that BGL (71.25±2.22 vs. 95.60±3.36 mg/dl, corticosterone level (24.33±4.23 vs. 36.9±2.01 ng/ml, acrosome reacted sperm (3.25±1.55 vs. 17.71±5.03%, and sperm head abnormality (3.29±0.71 vs. 6.21±1.18% were significantly higher in CS group in comparison with control. In contrast, seminal vesicle (0.41±0.05 vs. 0.24±0.07 g/100g, testosterone level (3.37±0.79 vs. 0.61±0.29 ng/ml, and sperm concentration (115.33±7.70 vs. 79.13±3.65×106 cells/ml of CS were significantly lower (p<0.05 than controls. Some atrophic seminiferous tubules and low sperm mass were apparent in CS rats. The expression of CYP11A1 except StAR protein was markedly decreased in CS rats. In contrast, a 55 kDa phosphorylated protein was higher in CS testes. Conclusion: CS decreased the expression of CYP11A, resulting in decreased testosterone, and increased acrosome-reacted sperm, assumed to be the result of an increase of 55 kDa phosphorylated protein.

Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

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Perez-Urrutia, Nelson; Mendoza, Cristhian; Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Echeverria, Florencia; Grizzell, J Alex; Barreto, George E; Iarkov, Alexandre; Echeverria, Valentina

2017-09-01

Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP+ cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP+ cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

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Oliveira, Carla de; Oliveira, Cleverson Moraes de; de Macedo, Isabel Cristina; Quevedo, Alexandre S; Filho, Paulo Ricardo Marques; Silva, Fernanda Ribeiro da; Vercelino, Rafael; de Souza, Izabel C Custodio; Caumo, Wolnei; Torres, Iraci L S

2015-01-01

Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity.

Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

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Touyarot, K.; Sandi, C.

2002-01-01

Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

Effects of harmane during treadmill exercise on spatial memory of restraint-stressed mice.

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Nasehi, Mohammad; Shahini, Faezeh; Ebrahimi-Ghiri, Mohaddeseh; Azarbayjani, MohammadAli; Zarrindast, Mohammad-Reza

2018-06-08

Chronic stress induces hippocampal-dependent memory deficits, which can be counterbalanced with prolonged exercise. On the other hand, the β-carboline alkaloid harmane exerts potential in therapies for Alzheimer's and depression diseases and modulating neuronal responses to stress. The present study investigated the effect of chronic treatment of harmane alone or during treadmill running on spatial memory deficit in restraint-stressed mice. To examine spatial memory, adult male NMRI mice were subjected to the Y-maze. Intraperitoneal administration of harmane (0.6 mg/kg, once/ 48 h for 25 days) decreased the percentage of time in the novel arm and the number of novel arm visits, indicating a spatial memory deficit. A 9-day restraint stress (3 h/day) also produced spatial learning impairment. However, a 4-week regime of treadmill running (10 m/min for 30 min/day, 5 days/week) aggravated the stress impairing effect on spatial learning of 3-day stressed mice compared to exercise/non-stressed mice. Moreover, harmane (0.3 mg/kg) associated with exercise increased the number of novel arm visits in 9-day stressed mice compared to harmane/exercise/non-stressed or 9-day stressed group. It should be noted that none of these factors alone or in combination with each other had no effect on locomotor activity. Taken together, these data suggest that there is no interaction between harmane and exercise on spatial memory in stress condition. Copyright © 2018. Published by Elsevier Inc.

Antagonism of corticotrophin-releasing factor receptors in the fourth ventricle modifies responses to mild but not restraint stress

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Miragaya, Joanna R.; Harris, Ruth B. S.

2008-01-01

Repeated restraint stress (RRS; 3 h of restraint on 3 consecutive days) in rodents produces temporary hypophagia, but a long-term downregulation of body weight. The mild stress (MS) of an intraperitoneal injection of saline and housing in a novel room for 2 h also inhibits food intake and weight gain, but the effects are smaller than for RRS. Previous exposure to RRS exaggerates hypophagia, glucocorticoid release, and anxiety-type behavior caused by MS. Here we tested the involvement of brain...

INTEGRATED QUANTITATIVE ASSESSMENT OF CHANGES IN NEURO-ENDOCRINE-IMMUNE COMPLEX AND METABOLISM IN RATS EXPOSED TO ACUTE COLD-IMMOBILIZATION STRESS

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Sydoruk O Sydoruk

2016-09-01

    Abstracts Background. It is known that the reaction of the neuroendocrine-immune complex to acute and chronic stress are different. It is also known about sex differences in stress reactions. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress at male rats. The purpose of this study - to carry out integrated quantitative estimation of neuroendocrine, immune and metabolic responses to acute stress at male and female rats. Material and research methods. The experiment is at 58 (28 male and 30 female white rats Wistar line weighing 170-280 g (Mean=220 g; SD=28 g. The day after acute (water immersion restraint stress determined HRV, endocrine, immune and metabolic parameters as well as gastric mucosa injuries and comparing them with parameters of intact animals. Results. Acute cold-immobilization stress caused moderate injuries the stomach mucosa as erosions and ulcers. Among the metabolic parameters revealed increased activity Acid Phosphatase, Asparagine and Alanine Aminotranspherase as well as Creatinephosphokinase. It was also found to reduce plasma Testosterone as well as serum Potassium and Phosphate probably due to increased Parathyrine and Mineralocorticoid activity and Sympathotonic shift of sympatho-vagal balance. Integrated quantitative measure manifestations of Acute Stress as mean of modules of Z-Scores makes for 10 metabolic parameters 0,75±0,10 σ and for 8 neuro-endocrine parameters 0,40±0,07 σ. Among immune parameters some proved resistant to acute stress factors, while 10 significant suppressed and 12 activated. Integrated quantitative measure poststressory changes makes 0,73±0,08 σ. Found significant differences integrated status intact males and females, whereas after stress differences are insignificant. Conclusion. The approach to integrated quantitative assessment of neuroendocrine-immune complex and metabolism may be useful for testing the

Different stress modalities result in distinct steroid hormone responses by male rats

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M.L. Andersen

2004-06-01

Full Text Available Since both paradoxical sleep deprivation (PSD and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming were applied twice a day, for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone, competitive immunoassay (progesterone and by radioimmunoassay (corticosterone, estradiol, estrone. The findings indicate that PSD (13.7 ng/dl, footshock (31.7 ng/dl and cold (35.2 ng/dl led to lower testosterone levels compared to the swimming (370.4 ng/dl and control (371.4 ng/dl groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml and PSD (5.4 ng/ml groups compared to control (1.6 ng/ml, swimming (1.1 ng/ml, cold (2.3 ng/ml, and restrained (1.2 ng/ml animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml and footshock (169.6 ng/ml groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.

Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

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Thiago B Kirsten

Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

The effect of synchronized running activity with chronic stress on passive avoidance learning and body weight in rats

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Maryam Radahmadi

2013-01-01

Results: Our results showed that: (1 Exercise under no stress provides beneficial effects on memory acquisition and retention time compared to Control group; especially retention time had significantly (P < 0.05 increased in exercised group. (2 Chronic stress with and without synchronized exercise significantly (P < 0.01, P < 0.05, respectively impaired acquisition and retention time. (3 Body weight differences were significantly (P < 0.01, P < 0.001 and P < 0.001 lower than Control group in exercise, stress and synchronized exercise with stress groups, respectively. (4 Adverse effects of restraint stress (psychical stress were probably greater than physical activity effects on learning, memory and weight loss. Conclusions: The data confirmed that synchronized exercise with stress had not significantly protective role in improvement of passive avoidance acquisition and retention time; hence it did not significantly improve learning and memory deficit in stressed rats; whereas exercise alone could improve memory deficit in rats.

Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

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Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

2011-08-03

Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

Induced dyadic stress and food intake: Examination of the moderating roles of body mass index and restraint.

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Côté, Marilou; Gagnon-Girouard, Marie-Pierre; Provencher, Véronique; Bégin, Catherine

2016-12-01

Restrained eaters and overweight and obese people are prone to increase their food intake during stressful situations. This study examines the impact of a stressful couple discussion on food intake in both spouses, while simultaneously taking into account the effect of BMI and restraint on this association. For 15min, 80 heterosexual couples discussed an aspect that they wanted their partner to change followed by an individual bogus taste test for the purpose of measuring his or her stress-induced food intake. Prior to and after the discussion, subjective mood state was assessed, as well as appetite perceptions, and the mood change before and after the discussion was calculated. Multiple regression analyses with a three-way interaction between mood change, BMI, and restraint were used to predict food intake for both men and women, while controlling for appetite perceptions. Only restrained women with a high BMI ate more when their mood worsened. For men, only appetite perceptions significantly predicted food intake. These results suggest that an induced negative mood in the form of a stressful couple discussion impacts food intake differently for men and women, and that particular attention should be given to the concomitant effect of both restraint and BMI when studying stress-induced eating among women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiovascular and metabolic consequences of the association between chronic stress and high-fat diet in rats.

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Simas, Bruna B; Nunes, Everson A; Crestani, Carlos C; Speretta, Guilherme F

2018-05-01

Obesity and chronic stress are considered independent risk factors for the development of cardiovascular diseases and changes in autonomic system activity. However, the cardiovascular consequences induced by the association between high-fat diet (HFD) and chronic stress are not fully understood. We hypothesized that the association between HFD and exposure to a chronic variable stress (CVS) protocol for four weeks might exacerbate the cardiovascular and metabolic disturbances in rats when compared to these factors singly. To test this hypothesis, male Wistar rats were divided into four groups: control-standard chow diet (SD; n = 8); control-HFD (n = 8); CVS-SD (n = 8); and CVS-HFD (n = 8). The CVS consisted of repeated exposure of the rats to different inescapable and unpredictable stressors (restraint tress; damp sawdust, cold, swim stress and light cycle inversion). We evaluated cardiovascular function, autonomic activity, dietary intake, adiposity and metabolism. The HFD increased body weight, adiposity and blood glucose concentration (∼15%) in both control and CVS rats. The CVS-HFD rats showed decreased insulin sensitivity (25%) compared to CVS-SD rats. The control-HFD and CVS-HFD rats presented increased intrinsic heart rate (HR) values (∼8%). CVS increased cardiac sympathetic activity (∼65%) in both SD- and HFD-fed rats. The HFD increased basal HR (∼10%). Blood pressure and baroreflex analyzes showed no differences among the experimental groups. In conclusion, the present data indicate absence of interaction on autonomic imbalance evoked by either CVS or HFD. Additionally, HFD increased HR and evoked metabolic disruptions which are independent of stress exposure.

Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

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Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

2016-01-01

Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

Plasma hormones facilitated the hypermotility of the colon in a chronic stress rat model.

Directory of Open Access Journals (Sweden)

Chengbai Liang

Full Text Available OBJECTIVE: To study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS, which mimics the irritable bowel syndrome (IBS. METHODS: Male Wistar rats were submitted daily to 1-h of water avoidance stress (WAS or sham WAS (SWAS for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique. RESULTS: The number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP, thyrotropin-releasing hormone (TRH, motilin (MTL, and cholecystokinin (CCK in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP, calcitonin gene-related peptide (CGRP and corticotropin releasing hormone (CRH in WAS rats were not significantly changed and peptide YY (PYY in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 µl decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 µl increased the amplitude of IKv and IBKCa in normal rats. CONCLUSION: These results suggest that WAS leads to changes of plasma hormones levels and to disordered myogenic colonic motility in the short term, but that the colon rapidly establishes a new equilibrium to maintain the normal baseline functioning.

Pro-oxidant effects in the brain of rats concurrently exposed to uranium and stress

International Nuclear Information System (INIS)

Linares, Victoria; Sanchez, Domenec J.; Belles, Montserrat; Albina, Luisa; Gomez, Mercedes; Domingo, Jose L.

2007-01-01

Metal toxicity may be associated with increased rates of reactive oxygen species (ROS) generation within the central nervous system (CNS). Although the kidney is the main target organ for uranium (U) toxicity, this metal can also accumulate in brain. In this study, we investigated the modifications on endogenous antioxidant capacity and oxidative damage in several areas of the brain of U-exposed rats. Eight groups of adult male rats received uranyl acetate dihydrate (UAD) in the drinking water at 0, 10, 20, and 40 mg/kg/day for 3 months. Animals in four groups were concurrently subjected to restraint stress during 2 h/day throughout the study. At the end of the experimental period, cortex, hippocampus and cerebellum were removed and processed to examine the following stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as U concentrations. The results show that U significantly accumulated in hippocampus, cerebellum and cortex after 3 months of exposure. Moreover, UAD exposure promoted oxidative stress in these cerebral tissues. In cortex and cerebellum, TBARS levels were positively correlated with the U content, while in cerebellum GSSG and GSH levels were positively and negatively correlated, respectively, with U concentrations. In hippocampus, CAT and SOD activities were positively correlated with U concentration. The present results suggest that chronic oral exposure to UAD can cause progressive perturbations on physiological brain levels of oxidative stress markers. Although at the current UAD doses restraint scarcely showed additional adverse effects, its potential influence should not be underrated

Effects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex.

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Negrón-Oyarzo, Ignacio; Pérez, Miguel Ángel; Terreros, Gonzalo; Muñoz, Pablo; Dagnino-Subiabre, Alexies

2014-02-01

The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic transmission in the prelimbic cortex during adulthood. Male Sprague Dawley rats were subjected to seven days of restraint stress on postnatal day forty-two (PND 42, adolescence). Afterward, the fear-conditioning paradigm was used to study conditioned fear extinction. Anxiety-like behavior was measured one day (PND 50) and twenty-one days (PND 70, adulthood) after stress using the elevated-plus maze and dark-light box tests, respectively. With another set of rats, excitatory synaptic transmission was analyzed with slices of the prelimbic cortex. Rats that had been stressed during adolescence and adulthood had higher anxiety-like behavior levels than did controls, while stress-induced slowing of learned fear extinction in adolescence was reversed during adulthood. As well, the field excitatory postsynaptic potentials of stressed adolescent rats had significantly lower amplitudes than those of controls, although the amplitudes were higher in adulthood. Our results demonstrate that short-term stress in adolescence induces strong effects on excitatory synaptic transmission in the prelimbic cortex and extinction of learned fear, where the effect of stress on anxiety is more persistent than on the extinction of learned fear. These data contribute to the understanding of stress neurobiology. Copyright © 2013 Elsevier B.V. All rights reserved.

Interactive effects of dietary restraint and adiposity on stress-induced eating and the food choice of children

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The Individual Differences Model posits that individual differences in physiological and psychological factors explain eating behaviors in response to stress. The purpose was to determine the effects of individual differences in adiposity, dietary restraint and stress reactivity on children's energy...

Activation of the HPA Axis and Depression of Feeding Behavior Induced by Restraint Stress Are Separately Regulated by PACAPergic Neurotransmission in the Mouse

OpenAIRE

Jiang, Sunny Zhihong; Eiden, Lee E.

2016-01-01

We measured serum CORT elevation in wild-type and PACAP-deficient C57Bl/6N male mice after acute (1 hr) or prolonged (2–3 hr) daily restraint stress for seven days. The PACAP-dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2 and 3 hr of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient m...

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

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Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

International Nuclear Information System (INIS)

Ribes, Diana; Fuentes, Silvia; Torrente, Margarita; Colomina, M. Teresa; Domingo, Jose L.

2010-01-01

Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats

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Malihe Sadeghi

2017-12-01

Full Text Available Objective(s: Cholecystokinin (CCK has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Materials and Methods: Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S was injected (1.6 µg/kg, IP before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization in order to investigate synaptic plasticity. Results: Stress impaired spatial memory significantly (P

The Effect of Synchronized Forced Running with Chronic Stress on Short, Mid and Long- term Memory in Rats.

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Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad-Reza; Hosseini, Nasrin

2013-03-01

Impairment of learning and memory processes has been demonstrated by many studies using different stressors. Other reports suggested that exercise has a powerful behavioral intervention to improve cognitive function and brain health. In this research, we investigated protective effects of treadmill running on chronic stress-induced memory deficit in rats. Fifty male Wistar rats were randomly divided into five groups (n=10) as follows: Control (Co), Sham (Sh), Stress (St), Exercise (Ex) and Stress and Exercise (St & Ex) groups. Chronic restraint stress was applied by 6h/day/21days and also treadmill running at a speed 20-21m/min for 1h/day/21days. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. OUR RESULTS SHOWED THAT: 1) Although exercise alone showed beneficial effects especially on short and mid-term memory (Pshort, mid and long-term memory deficit in stressed rats. 2) Short and mid-term memory deficit was significantly (PMemory deficit in synchronized exercise with stress group was nearly similar to stressed rats. 4) Helpful effects of exercise were less than harmful effects of stress when they were associated together. The data correspond to the possibility that although treadmill running alone has helpful effects on learning and memory consolidation, but when it is synchronized with stress there is no significant benefit and protective effects in improvement of memory deficit induced by chronic stress. However, it is has a better effect than no training on memory deficit in stressed rats.

Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

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Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

2018-04-01

The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chronic administration of caffeine and stress on feeding behavior of rats.

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Pettenuzzo, Leticia Ferreira; Noschang, Cristie; von Pozzer Toigo, Eduardo; Fachin, Andrelisa; Vendite, Deusa; Dalmaz, Carla

2008-10-20

Anorectic effects of caffeine are controversial in the literature, while stress and obesity are growing problems in our society. Since many stressed people are coffee drinkers, the objective of the present study was to evaluate the effect of stress and chronic administration of caffeine on feeding behavior and body weight in male and female rats. Wistar rats (both males and females) were divided into 3 groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated-restraint stress for 40 days). During the entire treatment, chow consumption was monitored and rats were weighed monthly. Afterwards, feeding behavior was evaluated during 3-min trials in food-deprived and ad libitum fed animals and also in repeated exposures, using palatable food (Froot Loops and Cheetos). Chronic administration of caffeine did not affect rat chow consumption or body weight gain, but diminished the consumption of both salty (Cheetos) and sweet (Froot Loops) palatable food. In the repeated trial tests, stress diminished savory snack consumption in the later exposures [I.S. Racotta, J. Leblanc, D. Richard The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system. Pharmacol Biochem Behav. 1994, 48:887-892; S.D. Comer, M. Haney, R.W. Foltin, M.W. Fischman Effects of caffeine withdrawal on humans living in a residential laboratory. Exp Clin Psychopharmacol. 1997, 5:399-403; A. Jessen, B. Buemann, S. Toubro, I.M. Skovgaard, A. Astrup The appetite-suppressant effect of nicotine is enhanced by caffeine. Diab Ob Metab. 2005, 7:327-333; J.M. Carney Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol. 1982, 75:451-454] and caffeine diminished consumption of both palatable foods (savory and sweet) during the early and later exposures. Most responses to caffeine were stronger

Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

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Tadashi Nakamura

2014-01-01

Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors.

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Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol

2013-08-01

Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats. Copyright © 2013 Elsevier B.V. All rights reserved.

Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals-relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats

DEFF Research Database (Denmark)

Aalling, Nadia; Hageman, Ida; Miskowiak, Kamilla Woznica

2018-01-01

. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2α...... and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus....

Task-specific compensation and recovery following focal motor cortex lesion in stressed rats.

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Kirkland, Scott W; Smith, Lori K; Metz, Gerlinde A

2012-03-01

One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

DEFF Research Database (Denmark)

Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

2002-01-01

OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

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Aloisi, A M; Steenbergen, H L; van de Poll, N E; Farabollini, F

1994-05-01

The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

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Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

2010-11-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

Effects of prenatal stress on anxiety- and depressive-like behaviors are sex-specific in prepubertal rats.

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Iturra-Mena, Ann Mary; Arriagada-Solimano, Marcia; Luttecke-Anders, Ariane; Dagnino-Subiabre, Alexies

2018-05-17

The fetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behavior. The aim of this study was to determine the physiological and behavioral effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 until 21, a critical period for fetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviors, and spontaneous social interaction. We also assessed maternal behaviors and two stress markers: basal vs. acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behavior, while both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation as well as anxiety- and depressive-like behaviors were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on the hypothalamus-pituitary-adrenal (HPA) axis activity and on behavior during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, as well as they were more anxious and experienced depressive-like behaviors. Our results can be useful to study the neurobiological basis of childhood depression at a pre-clinical level. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of different timing of stress on corticosterone, BDNF and memory in male rats.

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Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-02-01

Learning and memory seem to be affected by chronic stress. Previous reports have considered chronic stress as a precipitating factor of different neuropsychological disorders, while others reported neurobiological adaptations following stress. The present study investigated the effects of chronic stress before, after, and during learning on the changes of learning and memory, on serum and hippocampal levels of corticosterone (CORT), brain-derived neurotrophic factor (BDNF) and body weight in rats. Male Wistar rats were randomly divided into four groups (n=10) including Control (Co), Stress-Learning-Rest (St-L-Re), Rest-Learning-Stress (Re-L-St), and Stress-Learning-Stress (St-L-St) groups. The chronic restraint stress was applied 6 h/day for 21 days. Moreover, the passive avoidance test was used to assess memory deficit, 1, 7, and 21 days after training. At the end of experiments, CORT and BDNF levels were measured. The findings did not support adaptation in chronic stress conditions. The acquisition time as well as the short and mid-term memories was significantly impaired in the St-L-Re group. Short, mid, and long-term memories were significantly impaired in the Re-L-St and St-L-St groups compared with the Co group, as a result of the enhancement of CORT and reduction of BDNF levels. In the St-L-St group, changes in memory functions were less pronounced than in the Re-L-St group. Also, body weight declined following the chronic stress, while recovery period enhanced the body weight gain in stressed rats. It can be concluded that a potential time-dependent involvement of stress and recovery period on the level of BDNF. Longer duration time of chronic stress might promote adaptive effects on memory and CORT level. Copyright © 2014 Elsevier Inc. All rights reserved.

INCREASES IN ANXIETY-LIKE BEHAVIOR INDUCED BY ACUTE STRESS ARE REVERSED BY ETHANOL IN ADOLESCENT BUT NOT ADULT RATS

OpenAIRE

Varlinskaya, Elena I.; Spear, Linda P.

2011-01-01

Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnata...

Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice.

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Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

2014-04-03

Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

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Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

2011-01-01

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

Effects of prenatal exposure to chronic mild stress and toluene in rats

DEFF Research Database (Denmark)

Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

2005-01-01

The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

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Meerlo, P.; Koehl, M.; van der Borght, K.; Turek, F. W.

2002-01-01

Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems. However, few attempts have been made to examine how sleep loss affects the HPA axis response to subsequent stressors. Furthermore, most studies applied short-lasting total sleep deprivation and not restriction of sleep over a longer period of time, as often occurs in human society. Using the rat as our model species, we investigated: (i) the HPA axis activity during and after sleep deprivation and (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor. In one experiment, rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Control rats were placed in nonrotating wheels. In a second experiment, rats were subjected to an 8-day sleep restriction protocol allowing 4 h of sleep each day. To test the effects of sleep loss on subsequent stress reactivity, rats were subjected to a 30-min restraint stress. Blood samples were taken at several time points and analysed for adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH and corticosterone concentrations were elevated during sleep deprivation but returned to baseline within 4 h of recovery. After 1 day of sleep restriction, the ACTH and corticosterone response to restraint stress did not differ between control and sleep deprived rats. However, after 48 h of total sleep deprivation and after 8 days of restricted sleep, the ACTH response to restraint was significantly reduced whereas the corticosterone response was unaffected. These results show that sleep loss not only is a mild activator of the HPA axis itself, but also affects the subsequent response to stress. Alterations in HPA axis regulation may gradually appear under

Protective effect of Momordica charantia water extract against liver injury in restraint-stressed mice and the underlying mechanism.

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Deng, Yuanyuan; Tang, Qin; Zhang, Yan; Zhang, Ruifen; Wei, Zhencheng; Tang, Xiaojun; Zhang, Mingwei

2017-01-01

Background : Momordica charantia is used in China for its jianghuo (heat-clearing and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo , excessive internal heat) in traditional Chinese medicine is considered a type of stress response of the body. The stress process involves internal organs, especially the liver. Objective : We hypothesized that Momordica charantia water extract (MWE) has a hepatoprotective effect and can protect the body from stress. The aim of this study was to investigate the possible effects of MWE against liver injury in restraint-stressed mice. Design : The mice were intragastrically administered with MWE (250, 500 and 750 mg/kg bw) daily for 7 days. The Normal Control (NC) and Model groups were administered distilled water. A positive control group was intragastrically administered vitamin C 250 mg/kg bw. After the last administration, mice were restrained for 20 h. Results : MWE reduced the serum AST and ALT, reduced the NO content and the protein expression level of iNOSin the liver; significantly reduced the mitochondrial ROS content, increased the mitochondrial membrane potential and the activities of mitochondrial respiratory chain complexes I and II in restraint-stressed mice. Conclusions : The results indicate that MWE has a protective effect against liver injury in restraint-stressed mice. Abbreviations : MWE: Momordica charantia water extract; M. charantia: Momordica charantia L.; ROS: reactive oxygen species; NO: nitric oxide; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1 beta; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; IFN-γ: interferon gamma; VC: vitamin C; ALT: alanine transaminase; AST: aspartate aminotransferase; GSH: glutathione; GSH-PX: glutathione peroxidase; MDA: malondialdehyde; BCA: bicinchoninic acid; TBARS: thiobarbituric acid reactive substances; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; JC-B: Janus Green B; DW: dry weight; FC: Folin

Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

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Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

2012-11-01

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.

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Montes, Pedro; Ruiz-Sánchez, Elizabeth; Calvillo, Minerva; Rojas, Patricia

2016-09-01

Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.

Assessment the effect of NO inhibition on hippocampal normetanephrine level in stress and non-stress conditions in adult male rats

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Hana Molahoveizeh

2016-01-01

Full Text Available Background: Nitric oxide (NO has a role in the regulation of neurotransmitters release such as norepinephrine, in the hippocampus.Normetanephrine (NMN is a metabolite of norepinephrine created by action of catechol-O-methyl transferase (COMT on norepinephrine. Several studies have shown that various stresses increased release of norepinephrine and its metabolites. Therefore in the present study, the role of Nitric oxide in regulation of norepinephrine release and its metabolism was investigated by administration of L-NAME (NO synthase inhibitor in stressed and non-stressed rats. Materials and Methods: For this purpose, 50 adult rats were divided into 10 groups, of which 5 groups were exposed to restraint stress while another 5 groups were without stress. These two set of groups included intact, saline and L-NAME (20, 40, 80 mg/kg. Thirty minutes after intraperituneal injection of L-NAME, brains removed, the hippocampus dissected, weighed, homogenized and centrifuged then amount of NMN measured by ELISA kit. Results: The results showed that in non-stressed condition amount of NMN were significantly increased in group that received L-NAME (80 mg/kg in comparison with other groups but in stress condition, amount of NMN was significantly decreased in groups that received L-NAME (20,40,80 mg/kg, in comparison with control and saline groups. Comparison between stress and non-stressed groups showed that stress alone cause an increase in amount of NMN in control and saline groups. Conclusion: In conclusion, NO synthesis inhibition produced opposite responses with respect to NMN amount in the presence or absence of stress, and probably L-NAME preventing the effect of stress on increasing NMN levels mediated by nitrergic pathway.

Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male Rats on the Experimental Model of Post-Traumatic Stress Disorder.

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Pivina, S G; Rakitskaya, V V; Akulova, V K; Ordyan, N E

2016-03-01

Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

Adaptation of the hypothalamic-pituitary-adrenal axis and glucose to repeated immobilization or restraint stress is not influenced by associative signals.

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Rabasa, Cristina; Delgado-Morales, Raúl; Muñoz-Abellán, Cristina; Nadal, Roser; Armario, Antonio

2011-02-02

Repeated exposure to the same stressor very often results in a reduction of some prototypical stress responses, namely those related to the hypothalamic-pituitary-adrenal (HPA) and sympatho-medullo-adrenal (SMA) axes. This reduced response to repeated exposure to the same (homotypic) stressor (adaptation) is usually considered as a habituation-like process, and therefore, a non-associative type of learning. However, there is some evidence that contextual cues and therefore associative processes could contribute to adaptation. In the present study we demonstrated in two experiments using adult male rats that repeated daily exposure to restraint (REST) or immobilization on boards (IMO) reduced the HPA (plasma levels of ACTH and corticosterone) and glucose responses to the homotypic stressor and such reduced responses remained intact when all putative cues associated to the procedure (experimenter, way of transporting to the stress room, stress boxes, stress room and colour of the restrainer in the case of REST) were modified on the next day. Therefore, the present results do not favour the view that adaptation after repeated exposure to a stressor may involve associative processes related to signals predicting the imminence of the stressors, but more studies are needed on this issue. Copyright © 2010 Elsevier B.V. All rights reserved.

Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility.

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West, C; Wu, R Y; Wong, A; Stanisz, A M; Yan, R; Min, K K; Pasyk, M; McVey Neufeld, K-A; Karamat, M I; Foster, J A; Bienenstock, J; Forsythe, P; Kunze, W A

2017-01-01

Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1 ™ . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.

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Korczeniewska, Olga Anna; Khan, Junad; Tao, Yuanxiang; Eliav, Eli; Benoliel, Rafael

2017-01-01

To investigate the effects and interactions of sex and stress (provoked by chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal neuropathic pain. The effects of sex and RS (carried out for 14 days as a model for stress) on somatosensory measures (reaction to pinprick, von Frey threshold) in a rat model of trigeminal neuropathic pain were examined. The study design was 2 × 4, with surgery (pain) and sham surgery (no pain) interacting with male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the animals in each sex group underwent RS, and the remaining half were left unstressed. Following the RS period, trigeminal neuropathic pain was induced by unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the animals in the RS group and half in the nRS group (both males and females) were exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze (EPM) assessment and plasma interferon gamma (IFN-γ) levels were used to measure the effects of RS. Analysis of variance (ANOVA) was used to assess the effects of stress, sex, and their interactions on plasma IFN-γ levels, changes in body weight, EPM parameters, tactile allodynia, and mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc test corrected for multiple comparisons. Both male and female RS rats showed significantly altered exploratory behavior (as measured by EPM) and had significantly lower plasma IFN-γ levels than nRS rats. Rats exposed to RS gained weight significantly slower than the nRS rats, irrespective of sex. Following RS but before surgery, RS rats showed significant bilateral reductions in von Frey thresholds and significantly increased pinprick response difference scores compared to nRS rats, irrespective of sex. From 17 days postsurgery, RSIOCCI rats showed significantly reduced von Frey thresholds and

Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex.

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MacDowell, Karina S; Sayd, Aline; García-Bueno, Borja; Caso, Javier R; Madrigal, José L M; Leza, Juan Carlos

2017-09-01

Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.

Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

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Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

2013-11-01

Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

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Paulo Eduardo Carneiro de Oliveira

2016-09-01

Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

Central neuropeptide Y plays an important role in mediating the adaptation mechanism against chronic stress in male rats.

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Yang, Yu; Babygirija, Reji; Zheng, Jun; Shi, Bei; Sun, Weinan; Zheng, Xiaojiao; Zhang, Fan; Cao, Yu

2018-02-07

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress. Copyright © 2018 Endocrine Society.

Effects of stress and. beta. -funal trexamine pretreatment on morphine analgesia and opioid binding in rats

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Adams, J.U.; Andrews, J.S.; Hiller, J.M.; Simon, E.J.; Holtzman, S.G.

1987-12-28

This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opiods which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 yr or unstressed were injected ICV with either saline or 2.5 ..mu..g of ..beta..-funaltrexamine (..beta..-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia or were sacrificed and opioid binding in brain was determined. (/sup 3/H)D-Ala/sup 2/NMePhe/sup 4/-Gly/sup 5/(ol)enkephalin (DAGO) served as a specific ligand for mu-opioid receptors, and (/sup 3/H)-bremazocine as a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. ..beta..-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with ..beta..-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received ..beta..-FNA while unstressed. ..beta..-FNA caused small and similar decreases in (/sup 3/H)-DAGO binding in brain of both stressed and unstressed animals. 35 references, 2 figures, 2 tables.

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations.

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Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

2017-01-01

Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated

Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

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Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

2013-12-01

Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

Science.gov (United States)

Koizumi, So; Onozuka, Minoru

2015-01-01

The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior. PMID:26075223

Chewing prevents stress-induced hippocampal LTD formation and anxiety-related behaviors: a possible role of the dopaminergic system.

Science.gov (United States)

Ono, Yumie; Koizumi, So; Onozuka, Minoru

2015-01-01

The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

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Aricioglu, Feyza; Regunathan, Soundar

2010-01-01

Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

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Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

2012-01-01

Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

Acute stress induces selective alterations in cost/benefit decision-making.

Science.gov (United States)

Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

2012-09-01

Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1-3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression.

Alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats.

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Sun, Hongli; Su, Qian; Zhang, Huifang; Liu, Weimin; Zhang, Huiping; Ding, Ding; Zhu, Zhongliang; Li, Hui

2015-06-01

To clarify the alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats. We investigated the impact of prenatal restraint stress on the hipocampal cell proliferation in the progeny with 5-bromo-2'-deoxyuridine (BrdU), which is a marker of proliferating cells and their progeny. In addition, we observed the differentiation of neural stem cells (NSCs) with double labeling of BrdU/neurofilament (NF), BrdU/glial fibrillary acidic protein (GFAP) in the hipocampus. Prenatal stress (PS) increased cell proliferation in the dentate gyrus (DG) only in female and neuron differentiation of newly divided cells in the DG and CA4 in both male and female. Moreover, the NF and GFAP-positive cells, but not the BrdU-positive cells, BrdU/NF and BrdU/GFAP-positive cells, were found frequently in the CA3 and CA1 in the offspring of each group. These results possibly suggest a compensatory adaptive response to neuronal damage or loss in hippocampus induced by PS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Hypertensive response to stress: the role of histaminergic H1 and H2 receptors in the medial amygdala.

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de Almeida, Daniela Oliveira; Ferreira, Hilda Silva; Pereira, Luana Bomfim; Fregoneze, Josmara Bartolomei

2015-05-15

Different brain areas seem to be involved in the cardiovascular responses to stress. The medial amygdala (MeA) has been shown to participate in cardiovascular control, and acute stress activates the MeA to a greater extent than any of the other amygdaloid structures. It has been demonstrated that the brain histaminergic system may be involved in behavioral, autonomic and neuroendocrine responses to stressful situations. The aim of the present study was to investigate the role of the histaminergic receptors H1 and H2 in cardiovascular responses to acute restraint stress. Wistar rats (280-320g) received bilateral injections of cimetidine, mepyramine or saline into the MeA and were submitted to 45min of restraint stress. Mepyramine microinjections at doses of 200, 100 and 50nmol promoted a dose-dependent blockade of the hypertensive response induced by the restraint stress. Cimetidine (200 and 100nmol) promoted a partial blockade of the hypertensive response to stress only at the highest dose administered. Neither drugs altered the typical stress-evoked tachycardiac responses. Furthermore, mepyramine and cimetidine were unable to modify the mean arterial pressure or heart rate of freely moving rats under basal conditions (non-stressed rats). The data suggest that in the MeA the histaminergic H1 receptors appear to be more important than H2 receptors in the hypertensive response to stress. Furthermore, there appears to be no histaminergic tonus in the MeA controlling blood pressure during non-stress conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Subchronic mild noise stress increases HRP permeability in rat small intestine in vitro.

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Bijlsma, P B; van Raaij, M T; Dobbe, C J; Timmerman, A; Kiliaan, A J; Taminiau, J A; Groot, J A

2001-05-01

Recently we reported an increased trans- and paracellular protein permeability in rat small intestine after acute cold restraint stress. In the present study, we applied randomized 95- or 105-dB white noise pulses during 45 min/h, 12 h/day, duration 8 days, as a milder, but more chronic stressor to male rats. At 8 days before the noise experiments, 50% of the animals were cannulated in the vena cava for blood sampling during the experimental period. The other 50% of the animals were sacrificed at Day 9, segments of ileum were mounted in Ussing chambers and perfused at 37 degrees C. Horseradish peroxidase (HRP) was added mucosally, serosal appearance was detected enzymatically and tissues were fixed for electron microscopy. In the animals exposed to 95-dB noise, plasma corticosterone levels were enhanced twofold compared to controls, and ileal HRP flux was enhanced twofold. Electron micrographs of tissue from stressed or control animals showed no detectable paracellular staining of HRP. Quantification of HRP-containing endosomes in enterocytes revealed a twofold increase in endosome number in the animals exposed to 95-db noise indicating that the increased HRP permeability was primarily due to increased endocytosis. In contrast to the animals exposed to 95-dB noise, rats exposed to 105-dB noise showed no increase in corticosterone levels and ileal HRP fluxes were not significantly different from controls. We conclude that mild subchronic noise stress may cause a decrease in intestinal barrier function by increased transcytosis of luminal antigens.

Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats.

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Harper, Kathryn M; Knapp, Darin J; Park, Meredith A; Breese, George R

2017-01-01

Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats. Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays. Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults. Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.

Stress coping style does not determine social status, but influences the consequences of social subordination stress.

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Boersma, Gretha J; Smeltzer, Michael D; Scott, Karen A; Scheurink, Anton J; Tamashiro, Kellie L; Sakai, Randall R

2017-09-01

Chronic stress exposure may have negative consequences for health. One of the most common sources of chronic stress is stress associated with social interaction. In rodents, the effects of social stress can be studied in a naturalistic way using the visual burrow system (VBS). The way an individual copes with stress, their "stress coping style", may influence the consequences of social stress. In the current study we tested the hypothesis that stress coping style may modulate social status and influence the consequences of having a lower social status. We formed 7 VBS colonies, with 1 proactive coping male, 1 passive coping male, and 4 female rats per colony to assess whether a rat's coping style prior to colony formation could predict whether that individual is more likely to become socially dominant. The rats remained in their respective colonies for 14days and the physiological and behavioral consequences of social stress were assessed. Our study shows that stress coping style does not predict social status. However, stress coping style may influence the consequences of having a lower social status. Subordinate passive and proactive rats had distinctly different wound patterns; proactive rats had more wounds on the front of their bodies. Behavioral analysis confirmed that proactive subordinate rats engaged in more offensive interactions. Furthermore, subordinate rats with a proactive stress coping style had larger adrenals, and increased stress responsivity to a novel acute stressor (restraint stress) compared to passive subordinate rats or dominant rats, suggesting that the allostatic load may have been larger in this group. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats.

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Sadeghi, Malihe; Reisi, Parham; Radahmadi, Maryam

2017-12-01

Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long-term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity. Stress impaired spatial memory significantly ( P stress group. With respect to the control group, both fEPSP amplitude and slope were significantly ( P stress group. However, there were no differences between responses of the control-CCK and Stress-CCK groups compared to the control group. The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

International Nuclear Information System (INIS)

Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

1986-01-01

Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development

Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

Directory of Open Access Journals (Sweden)

Yumie Ono

2015-01-01

Full Text Available The present study examined the effects of chewing on stress-induced long-term depression (LTD and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

Science.gov (United States)

Macedo, I C; Rozisky, J R; Oliveira, C; Oliveira, C M; Laste, G; Nonose, Y; Santos, V S; Marques, P R; Ribeiro, M F M; Caumo, W; Torres, I L S

2015-06-01

Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels. Copyright © 2015. Published by Elsevier Ltd.

Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

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Kuswati

2015-04-01

Full Text Available Background Stress is one of the factors that cause apoptosis in neuronal cells. Centella asiatica has a neuroprotective effect that can inhibit apoptosis. This study aimed to examine the effect of Centella asiatica ethanol extract on B-cell lymphoma 2 (Bcl-2 protein expression in the prefrontal cortex of rats. Methods An experimental study was conducted on 34 brain tissue samples from male Sprague Dawley rats exposed to chronic restraint stress for 21 days. The samples were taken from following groups: non-stress group K, negative control group P1 (stress + arabic gum powder, P2 (stress + C.asiatica at 150 mg/kgBW, P3 (stress + C.asiatica at 300 mg/kg BW, P4 (stress + C.asiatica at 600 mg/kg body weight and positive control group P5 (stress + fluoxetine at 10 mg/kgBW. The samples were made into sections that were stained immunohistochemically using Bcl-2 antibody to determine the percentage of cells expressing Bcl-2. Data were analyzed using one way ANOVA test followed by a post - hoc test. Results There were significant differences in mean Bcl-2 expression between the groups receiving Centella asiatica compared with the non-stress group and stress-only group (negative control group (p<0.05. The results were comparable to those of the fluoxetine treatment group. Conclusion The Centella asiatica ethanol extract was able to increase Bcl-2 expression in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress. This study suggests that Centella asiatica may be useful in the treatment of cerebral stress.

Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.

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Chandranath, S I; Bastaki, S M A; D'Souza, A; Adem, A; Singh, J

2011-03-01

Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats.

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Li, Xiao-Heng; Liu, Neng-Bao; Zhang, Min-Hai; Zhou, Yan-Ling; Liao, Jia-Wan; Liu, Xiang-Qian; Chen, Hong-Wei

2007-04-20

The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P < 0.05). The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group (P < 0.05). The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group (P < 0.05). Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may

Studies on toxicity, anti-stress and hepato-protective properties of Kombucha tea.

Science.gov (United States)

Pauline, T; Dipti, P; Anju, B; Kavimani, S; Sharma, S K; Kain, A K; Sarada, S K; Sairam, M; Ilavazhagan, G; Devendra, K; Selvamurthy, W

2001-09-01

The objective of the study was to evaluate toxicity, anti-stress activity and hepato-protective properties of Kombucha tea. Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti-stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. The effect of oral administration of different doses of K-tea to albino rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats. K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly. The study shows that K-tea has anti-stress and hepato-protective activities.

Modulation of OCT3 expression by stress, and antidepressant-like activity of decynium-22 in an animal model of depression.

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Marcinkiewcz, C A; Devine, D P

2015-04-01

The organic cation transporter-3 (OCT3) is a glucocorticoid-sensitive uptake mechanism that has been shown to regulate the bioavailability of monoamines in brain regions that are implicated in the pathophysiology of depression. In the present study, the relative impacts of acute stress alone and acute stress with a history of repeated stress (chronic+acute) were evaluated in two strains of rats: the stress-vulnerable Wistar-Kyoto (WKY) strain and the somewhat more stress-resilient Long-Evans (LE) strain. OCT3 mRNA was significantly upregulated in the hippocampus of LE rats 2h after exposure to acute restraint stress, but not in acutely-restrained rats with a history of repeated social defeat stress. WKY rats exhibited a very different pattern. OCT3 mRNA was unaffected by acute restraint stress alone but was robustly upregulated after repeated+acute stress. There was also a corresponding increase in cytosolic OCT3 protein following repeated+acute stress in WKY rats 3h after presentation of the acute stressor. These results are consistent with the hypothesis that altered expression of the OCT3 may play a role in stress coping, and strain differences in regulation of this expression may contribute to differences in physiological and behavioral responses to stress. Furthermore, the OCT3 inhibitor, decynium 22 (1 and 10μg/kg, i.p.) reduced immobility of WKY rats, but not that of LE rats, in the forced swim test, suggesting that blockade of the OCT3 has antidepressant-like effects. Since WKY rats also appear to be resistant to the behavioral effects of traditional antidepressants, this also suggests that OCT3 antagonism may be an alternative therapeutic strategy for the treatment of depression in individuals who do not respond to conventional antidepressants. Published by Elsevier Inc.

Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

International Nuclear Information System (INIS)

Wang, Bing; Tanaka, Kaoru; Katsube, Takanori; Ninomiya, Yasuharu; Vares, Guillaume; Nakajima, Tetsuo; Nenoi, Mitsuru; Liu Qiang; Morita, Akinori

2015-01-01

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. (author)

Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

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Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

2011-10-24

Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of chronic mild stress on parameters of bone assessment in adult male and female rats

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Fabrício L. Valente

Full Text Available Abstract: Osteoporosis is a multifactorial disease of high prevalence and has great impact on quality of life, because the effects on bone structure increase the risk of fractures, what may be very debilitating. Based on the observation that patients with depression have lower bone mineral density than healthy individuals, many studies have indicated that stress could be an aggravating factor for bone loss. This study evaluates the effect of a protocol of chronic mild stress (CMS on parameters of bone assessment in male and female rats. Five 5-monh-old rats of each sex underwent a schedule of stressor application for 28 days. Stressors included cold, heat, restraint, cage tilt, isolation, overnight illumination, and water and food deprivation. Five rats of each sex were kept under minimum intervention as control group. The animals were weighed at beginning and end of the period, and after euthanasia had their bones harvested. Femur, tibia and lumbar vertebrae were analyzed by bone densitometry. Biomechanical tests were performed in femoral head and diaphysis. Trabecular bone volume was obtained from histomorphometric analysis of femoral head and vertebral body, as well as of femoral midshaft cross-sectional measures. Not all parameters analyzed showed effect of CMS. However, tibial and L4 vertebral bone mineral density and cross-sectional cortical/medullar ratio of femoral shaft were lower in female rats submitted to the CMS protocol. Among male rats, the differences were significant for femoral trabecular bone volume and maximum load obtained by biomechanical test. Thus, it could be confirmed that CMS can affect the balance of bone homeostasis in rats, what may contribute to the establishment of osteopenia or osteoporosis.

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

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Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

2015-06-01

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

Chronic Stress Impairs Prefrontal Cortex-Dependent Response Inhibition and Spatial Working Memory

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Mika, Agnieszka; Mazur, Gabriel J.; Hoffman, Ann N.; Talboom, Joshua S.; Bimonte-Nelson, Heather A.; Sanabria, Federico; Conrad, Cheryl D.

2012-01-01

Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

Social exclusion intensifies anxiety-like behavior in adolescent rats.

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Lee, Hyunchan; Noh, Jihyun

2015-05-01

Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.

Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

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Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza

2016-10-01

The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1β and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1β and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

The effect of basolateral amygdala nucleus lesion on memory under acute,mid and chronic stress in male rats.

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Ranjbar, Hoda; Radahmadi, Maryam; Alaei, Hojjatallah; Reisi, Parham; Karimi, Sara

2016-12-20

The basolateral amygdala (BLA) modulates memory for emotional events and is involved in both stress and memory. This study investigated different durations of stress and the role of BLA on serum corticosterone level and spatial and cognitive memory. Different durations of stress (acute, mid, and chronic stress), with and without BLA lesion were induced in rats by 6 h/day restraint stress for 1, 7, and 21 days. Memory functions were evaluated by novel object recognition (NOR) and object location test (OLT). The OLT findings showed locomotor activity and spatial memory slightly decreased with different durations of stress. The NOR findings significantly showed locomotor activity impairment in different durations of stress. Cognitive memory deficit was observed in mid stress. The corticosterone level significantly increased in the mid and chronic stress groups. Moreover, the mid stress was the strongest stress condition. There is a possibility that different stress durations act by different mechanisms. The recognition of a novel location decreased in all lesion groups. It was more severe in the NOR. The BLA lesion significantly decreased corticosterone level in the mid and chronic stress groups compared to similar groups without lesion. The BLA lesion caused more damage to cognitive than spatial memory in stressed groups.

Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety.

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Taukulis, H K; Goggin, C E

1990-03-01

On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.

Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

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Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

2014-07-01

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by "Silencing" Central Glucagon-Like Peptide 1 Signaling in Rats.

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Maniscalco, James W; Zheng, Huiyuan; Gordon, Patrick J; Rinaman, Linda

2015-07-29

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. The results from this study reveal a potential central mechanism for the "metabolic tuning" of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats, reduces or blocks the ability of

Influence of adrenal hormones in the occurrence and prevention of stress ulcers.

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Yigiter, Murat; Albayrak, Yavuz; Polat, Beyzagul; Suleyman, Bahadır; Salman, Ahmet Bedii; Suleyman, Halis

2010-11-01

The aim of the study was to examine whether endogenous cortisol and adrenalin have a role in the formation of stress ulcers in intact and adrenalectomized rats. The study was composed of 4 experiments: ulcerated areas in stomachs of adrenalectomized and intact rats were measured, adrenaline (100 μg/kg) and prednisolone (5 mg/kg) were injected intraperitoneally in adrenalectomized rats, metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered to intact rats, and metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered orally with yohimbine (10 mg/kg) and yohimbine (10 mg/kg) alone were administered to intact rats. After 24-hour restraint stress, ulcerated areas were measured. In the stomach of intact rats, the degree of stress ulcer was 7.25 times more severe than that noted in adrenalectomized rats. Furthermore, stress ulcers in adrenalectomized rats that received adrenaline or prednisolone only were fewer and less severe than rats receiving both adrenaline and prednisolone. Simultaneous administration of adrenaline and prednisolone did not prevent the formation of stress ulcers. However, either of these hormones alone (adrenaline or prednisolone), in the absence of the other, repressed the formation of stress ulcers. This antiulcer activity may be related to α2-adrenergic receptor activity. Copyright © 2010 Elsevier Inc. All rights reserved.

The effect of restraints type on the generated stresses in gantry crane beam

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Sowa Leszek

2018-01-01

Full Text Available This paper includes an analysis of the mechanical phenomena in the gantry crane beam, because the cranes are currently one of the most common devices for the transporting loads. Designing modern mechanical structures is a complex task that requires the use of appropriate tools. Such a modern tool is the numerical simulation, which uses different numerical methods. One of the best known methods is the finite element method, also used here. Simulations are limited to analysis of the strength of the gantry crane beam that was the loaded of the force load movement along its length. The numerical analysis was made to the gantry crane beam which cross-section was an I-beam and ends were fixed in different ways. As the result of numerical calculations, the stresses and displacements of the structure of gantry were obtained. The influence of the restraints type and changing the loading force position on generate the Huber-Misses stress in the gantry crane beam was estimated. The aim was to ensure that the maximum equivalent stress generated in the gantry crane beam was less than the strength of material, because then the construction is safe.

Distinct actions of ancestral vinclozolin and juvenile stress on neural gene expression in the male rat

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Ross eGillette

2015-03-01

Full Text Available Exposure to the endocrine disrupting chemical vinclozolin during gestation of an F0 generation and/or chronic restraint stress during adolescence of the F3 descendants affects behavior, physiology, and gene expression in the brain. Genes related to the networks of growth factors, signaling peptides and receptors, steroid hormone receptors and enzymes, and epigenetic related factors were measured using quantitative polymerase chain reaction via Taqman low density arrays targeting 48 genes in the central amygdaloid nucleus, medial amygdaloid nucleus, medial preoptic area, lateral hypothalamus, and the ventromedial nucleus of the hypothalamus. We found that growth factors are particularly vulnerable to ancestral exposure in the central and medial amygdala; restraint stress during adolescence affected neural growth factors in the medial amygdala. Signaling peptides were affected by both ancestral exposure and stress during adolescence primarily in hypothalamic nuclei. Steroid hormone receptors and enzymes were strongly affected by restraint stress in the medial preoptic area. Epigenetic related genes were affected by stress in the ventromedial hypothalamus and by both ancestral exposure and stress during adolescence independently in the central amygdala. It is noteworthy that the lateral hypothalamus showed no effects of either manipulation. Gene expression is discussed in the context of behavioral and physiological measures previously published.

Distinct actions of ancestral vinclozolin and juvenile stress on neural gene expression in the male rat.

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Gillette, Ross; Miller-Crews, Isaac; Skinner, Michael K; Crews, David

2015-01-01

Exposure to the endocrine disrupting chemical vinclozolin during gestation of an F0 generation and/or chronic restraint stress during adolescence of the F3 descendants affects behavior, physiology, and gene expression in the brain. Genes related to the networks of growth factors, signaling peptides, and receptors, steroid hormone receptors and enzymes, and epigenetic related factors were measured using quantitative polymerase chain reaction via Taqman low density arrays targeting 48 genes in the central amygdaloid nucleus, medial amygdaloid nucleus, medial preoptic area (mPOA), lateral hypothalamus (LH), and the ventromedial nucleus of the hypothalamus. We found that growth factors are particularly vulnerable to ancestral exposure in the central and medial amygdala; restraint stress during adolescence affected neural growth factors in the medial amygdala. Signaling peptides were affected by both ancestral exposure and stress during adolescence primarily in hypothalamic nuclei. Steroid hormone receptors and enzymes were strongly affected by restraint stress in the mPOA. Epigenetic related genes were affected by stress in the ventromedial nucleus and by both ancestral exposure and stress during adolescence independently in the central amygdala. It is noteworthy that the LH showed no effects of either manipulation. Gene expression is discussed in the context of behavioral and physiological measures previously published.

Increased depression-like behaviors with dysfunctions in the stress axis and the reward center by free access to highly palatable food.

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Park, E; Kim, J Y; Lee, J-H; Jahng, J W

2014-03-14

This study was conducted to examine the behavioral consequences of unlimited consumption of highly palatable food (HPF) and investigate its underlying neural mechanisms. Male Sprague-Dawley rats had free access to chocolate cookie rich in fat (HPF) in addition to ad libitum chow and the control group received chow only. Rats were subjected to behavioral tests during the 2nd week of food condition; i.e. ambulatory activity test on the 8th, elevated plus maze test (EPM) on the 10th and forced swim test (FST) on the 14th day of food condition. After 8 days of food condition, another group of rats were placed in a restraint box and tail bloods were collected at 0, 20, 60, and 120 time points during 2h of restraint period, used for the plasma corticosterone assay. At the end of restraint session, rats were sacrificed and the tissue sections of the nucleus accumbens (NAc) were processed for c-Fos immunohistochemistry. Ambulatory activities and the scores of EPM were not significantly affected by unlimited cookie consumption. However, immobility duration during FST was increased, and swim decreased, in the rats received free cookie access compared with control rats. Stress-induced corticosterone increase was exaggerated in cookie-fed rats, while the stress-induced c-Fos expression in the NAc was blunted, compared to control rats. Results suggest that free access to HPF may lead to the development of depression-like behaviors in rats, likely in relation with dysfunctions in the hypothalamic-pituitary-adrenal axis and the reward center. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus.

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Kim, Mun Hee; Leem, Yea Hyun

2014-03-01

Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model. To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behaviors were measured by forced swimming test (TST), and anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to 8. Restraint stress was started at week 6 week and ended at week 8. To elucidate the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in hippocampus using immunohistochemical technique. Chronic/repeated restraint stress induced behavioral anxiety and depression, such as reduced time and entries in open arms in EPM and enhanced immobility time in FST. These anxiety and depressive behaviors were ameliorated by chronic exercise. Also, these behavioral changes were concurrent with the deficit of 5HT1A and cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise. These results suggest that chronic exercise may improve the disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed brain, thereby exerting an antidepressive action.

Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

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Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

2017-03-01

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Different Forms of Hypokinesia on the Ultrastructure of Limbic, Extrapyramidal and Neocortical Areas of the Rat Brain: Electron Microscopic Study

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Zhvania, Mzia G.; Japaridze, Nadezhda J.; Ksovreli, Mariam G.

The effect of chronic restraint stress and chronic hypokinesia "without stress" on the ultrastructure of central and lateral nuclei of amygdala, CA1 and CA3 area of the hippocampus, cingular cortex, nucleus caudatus and motor cortex of adult male rats were elucidated. In some neurons and synapses of abovementioned regions pathological modifications were revealed. More significant alterations provokes chronic restraint stress. Alterations are mostly concentrated: first—in the nuclei of amygdala, then in the CA1 and CA3 areas. Moderate alterations were observed in cingular cortex and nucleus caudatus. In comparing with it, hypokinesia "without stress" provokes only moderate modifications: predominantly in the nucleus caudatus, in lesser degree—in the hippocampus and amygdalae.

Stress-induced changes in the expression of the clock protein PERIOD1 in the rat limbic forebrain and hypothalamus: role of stress type, time of day, and predictability.

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Sherin Al-Safadi

Full Text Available Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl and oval nucleus of the bed nucleus of the stria terminalis (BNSTov. Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN, the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms.

Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood.

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Varlinskaya, Elena I; Kim, Esther U; Spear, Linda P

2017-01-01

We previously observed lasting and sex-specific detrimental consequences of early adolescent intermittent ethanol exposure (AIE), with male, but not female, rats showing social anxiety-like alterations when tested as adults. The present study used Sprague Dawley rats to assess whether social alterations induced by AIE (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45) are further exacerbated by stressors later in life. Another aim was to determine whether AIE alone or in combination with stress influenced intake of a sweetened ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone (Experiment 2) under social circumstances. Animals were exposed to restraint on P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged after AIE in non-stressed males, but not females, whereas stress-induced social anxiety was evident only in water-exposed males and females. Adult-typical habituation of the CORT response to repeated restraint was not evident in adult animals after AIE, a lack of habituation reminiscent of that normally evident in adolescents. Neither AIE nor stress affected ethanol intake under social circumstances, although AIE and restraint independently increased adolescent-typical play fighting in males during social drinking. Among males, the combination of AIE and restraint suppressed "supersac" intake; this index of depression-like behavior was not seen in females. The results provide experimental evidence associating adolescent alcohol exposure, later stress, anxiety, and depression, with young adolescent males being particularly vulnerable to long-lasting adverse effects of repeated ethanol. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice

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Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Wörtwein, Gitta

2011-01-01

Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression......-like behaviour, NPY and galanin gene expression was studied in brains of mice subjected to chronic restraint stress (CRS) and concomitant treatment with the antidepressant fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour that was associated with increased NPY mRNA levels...... in the medial amygdala. Concomitant FLX treatment reverted depression-like effects of CRS and led to significant increases in levels of NPY and galanin mRNA in the dentate gyrus, amygdala, and piriform cortex. These findings suggest that effects on NPY and galanin gene expression could play a role...

Sex differences in the stress response in SD rats.

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Lu, Jing; Wu, Xue-Yan; Zhu, Qiong-Bin; Li, Jia; Shi, Li-Gen; Wu, Juan-Li; Zhang, Qi-Jun; Huang, Man-Li; Bao, Ai-Min

2015-05-01

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and β, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Social isolation alters central nervous system monoamine content in prairie voles following acute restraint.

Science.gov (United States)

McNeal, Neal; Anderson, Eden M; Moenk, Deirdre; Trahanas, Diane; Matuszewich, Leslie; Grippo, Angela J

2018-04-01

Animal models have shown that social isolation and other forms of social stress lead to depressive- and anxiety-relevant behaviors, as well as neuroendocrine and physiological dysfunction. The goal of this study was to investigate the effects of prior social isolation on neurotransmitter content following acute restraint in prairie voles. Animals were either paired with a same-sex sibling or isolated for 4 weeks. Plasma adrenal hormones and ex vivo tissue concentrations of monoamine neurotransmitters and their metabolites were measured following an acute restraint stressor in all animals. Isolated prairie voles displayed significantly increased circulating adrenocorticotropic hormone levels, as well as elevated serotonin and dopamine levels in the hypothalamus, and potentially decreased levels of serotonin in the frontal cortex. However, no group differences in monoamine levels were observed in the hippocampus or raphe. The results suggest that social stress may bias monoamine neurotransmission and stress hormone function to subsequent acute stressors, such as restraint. These findings improve our understanding of the neurobiological mechanisms underlying the consequences of social stress.

Mechanical restraint in psychiatry

DEFF Research Database (Denmark)

Bak, Jesper; Zoffmann, Vibeke; Sestoft, Dorte Maria

2014-01-01

PURPOSE: To examine how potential mechanical restraint preventive factors in hospitals are associated with the frequency of mechanical restraint episodes. DESIGN AND METHODS: This study employed a retrospective association design, and linear regression was used to assess the associations. FINDINGS......: Three mechanical restraint preventive factors were significantly associated with low rates of mechanical restraint use: mandatory review (exp[B] = .36, p mechanical...

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

Science.gov (United States)

Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

2018-05-26

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Akebia quinata Decaisne aqueous extract acts as a novel anti-fatigue agent in mice exposed to chronic restraint stress.

Science.gov (United States)

Park, Sun Haeng; Jang, Seol; Lee, Si Woo; Park, Sun Dong; Sung, Yoon-Young; Kim, Ho Kyoung

2018-08-10

Akebia quinata Decaisne extract (AQE; Lardizabalaceae) is used in traditional herbal medicine for stress- and fatigue-related depression, improvement of fatigue, and mental relaxation. To clarify the effects of AQE on stress-induced fatigue, we investigated the neuroprotective pharmacological effects of A. quinata Decaisne in mice exposed to chronic restraint stress. Seven-week old C57BL/6 mice chronically stressed by immobilization for 3 h daily for 15 d and non-stressed control mice underwent daily oral administration of AQE or distilled water. The open field, sucrose preference, and forced swimming behavioral tests were carried out once weekly, and immunohistochemical analyses of NeuN, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element-binding (CREB) protein, and BDNF receptor tropomyosin receptor kinase B (TrkB) in striatum and hippocampus were performed at the end of the experimental period. Brain levels of serotonin, adrenaline, and noradrenaline as well as serum levels of corticosterone were measured. Behavioral tests showed that treatment with AQE improved all lethargic behaviors examined. AQE significantly attenuated the elevated levels of adrenaline, noradrenaline, and serotonin in the brain and corticosterone, alanine transaminase, and aspartate transaminase levels in the serum. Histopathological analysis showed that AQE reduced liver injury and lateral ventricle size in restraint-stress mice via inhibition of neuronal cell death. Immunohistochemical analysis showed increased phosphorylation of CREB and expression of BDNF and its receptor TrkB in striatum and hippocampus. Chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C were identified as the primary components of AQE. All three agents increased expression of BDNF in SH-SY5Y cells and PC12 cells with H 2 O 2 -induced neuronal cell damage. AQE may have a neuroprotective effect and ameliorate the effects of stress and fatigue-associated brain damage through

Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

Science.gov (United States)

Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

2010-12-01

Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124.

Science.gov (United States)

Uphouse, Lynda; Hiegel, Cindy

2014-07-01

A brief restraint experience reduces lordosis behavior in ovariectomized females that have been hormonally primed with estradiol benzoate. The addition of progesterone to the priming prevents the lordosis inhibition. Based on prior studies with an inhibitor of progesterone metabolism, we have implicated the intracellular progesterone receptor, rather than progesterone metabolites, as responsible for this protection. However, the progesterone metabolite, allopregnanolone (3α-hydroxy-5α-pregnan-20-one), also prevents lordosis inhibition after restraint. In a prior study, we reported that the progestin receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), attenuated the effect of allopregnanolone. Because RU486 can also block the glucocorticoid receptor, in the current studies, we evaluated the effect of the progestin receptor antagonist, CDB-4124 (17α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione), which is relatively devoid of antiglucocorticoid activity. Ovariectomized, Fischer rats were injected with 10 μg estradiol benzoate. Two days later, rats received either 60 mg/kg CDB-4124 or 20% DMSO/propylene glycol vehicle 1 h before injection with 4 mg/kg allopregnanolone. After a pretest to confirm sexual receptivity, rats were restrained for 5min and immediately tested for sexual behavior. Lordosis behavior was reduced by the restraint and attenuated by allopregnanolone. Pretreatment with CDB-4124 reduced allopregnanolone's effect. These findings support prior suggestions that allopreganolone reduces the response to restraint by mechanisms that require activation of the intracellular progesterone receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

Science.gov (United States)

Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats.

Science.gov (United States)

Fride, E; Dan, Y; Feldon, J; Halevy, G; Weinstock, M

1986-01-01

This study investigated the hypotheses that unpredictable prenatal stress has effects on the offspring, similar to those induced by perinatal administration of glucocorticoids and increases the vulnerability to stressful situations at adulthood. Rats were exposed to random noise and light stress throughout pregnancy. Offspring were tested for the development of spontaneous alternation behavior (SA) and at adulthood, their response to novel or aversive situations, open field, extinction and punishment following acquisition of an appetitive response and two-way active avoidance, were assessed. In prenatally stressed rats, the development of SA was significantly delayed. On repeated exposure to an open field they were less active; control rats had elevated plasma corticosterone (CCS) on days 2 and 4 of open field exposure, while prenatally stressed rats had significantly raised plasma CCS after each exposure (days 1-8). Furthermore, punishment-induced suppression of an appetitive response was enhanced. Acquisition of active avoidance was faciliated in female but reduced in male prenatally stressed offspring. It is suggested that random prenatal noise and light stress may cause impairment of development of hippocampal function which lasts into adulthood. This impairment is manifested as an increase in vulnerability and a decrease in habituation to stressful stimuli.

Mechanical Restraint - Which Interventions Prevent Episodes of Mechanical Restraint? - A Systematic Review

DEFF Research Database (Denmark)

Bak, Jesper; Brandt-Christensen, Anne Mette; Sestoft, Dorte Maria

2012-01-01

PURPOSE:  To identify interventions preventing mechanical restraints. DESIGN AND METHODS:  Systematic review of international research papers dealing with mechanical restraint. The review combines qualitative and quantitative research in a new way, describing the quality of evidence and the effect...... of intervention. FINDINGS:  Implementation of cognitive milieu therapy, combined interventions, and patient-centered care were the three interventions most likely to reduce the number of mechanical restraints. PRACTICE IMPLICATIONS:  There is a lack of high-quality and effective intervention studies. This leaves...... patients and metal health professionals with uncertainty when choosing interventions in an attempt to prevent mechanical restraints....

ALLOPREGNANOLONE’S ATTENUATION OF THE LORDOSIS-INHIBITNG EFFECTS OF RESTRAINT IS BLOCKED BY THE ANTIPROGESTIN, CDB-4124

Science.gov (United States)

Uphouse, Lynda; Hiegel, Cindy

2014-01-01

A brief restraint experience reduces lordosis behavior in ovariectomized females that have been hormonally primed with estradiol benzoate. The addition of progesterone to the priming prevents the lordosis inhibition. Based on prior studies with an inhibitor of progesterone metabolism, we have implicated the intracellular progesterone receptor, rather than progesterone metabolites, as responsible for this protection. However, the progesterone metabolite, allopregnanolone (3α-hydroxy-5α-pregnan-20-one), also prevents lordosis inhibition after restraint. In a prior study, we reported that the progestin receptor antagonist, RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), attenuated the effect of allopregnanolone. Because RU486 can also block the glucocorticoid receptor, in the current studies, we evaluated the effect of the progestin receptor antagonist, CDB-4124 (17 α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione), which is relatively devoid of antiglucocorticoid activity. Ovariectomized, Fischer rats were injected with 10 μg estradiol benzoate. Two days later, rats received either 60 mg/kg CDB-4124 or the 20% DMSO/propylene glycol vehicle 1 hr before injection with 4 mg/kg allopregnanolone. After a pretest to confirm sexual receptivity, rats were restrained for 5 min and immediately tested for sexual behavior. Lordosis behavior was reduced by the restraint and attenuated by allopregnanolone. Pretreatment with CDB-4124 reduced allopregnanolone’s effect. These findings support prior suggestions that allopreganolone reduces the response to restraint by mechanisms that require activation of the intracellular progesterone receptor. PMID:24650591

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Science.gov (United States)

Noble, L J; Gonzalez, I J; Meruva, V B; Callahan, K A; Belfort, B D; Ramanathan, K R; Meyers, E; Kilgard, M P; Rennaker, R L; McIntyre, C K

2017-08-22

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

DEFF Research Database (Denmark)

Henningsen, Kim; Johannesen, Mads Dyrvig; Bouzinova, Elena

2012-01-01

In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

Stress triggers anhedonia in rats bred for learned helplessness.

Science.gov (United States)

Enkel, Thomas; Spanagel, Rainer; Vollmayr, Barbara; Schneider, Miriam

2010-05-01

Congenitally helpless (cLH) rats, a well-accepted model for depression, show reduced consumption of sweet solutions only under single-housing conditions, indicating anhedonia under stress. We investigated if anhedonic-like behaviour, measured by a reduction of sweetened-condensed milk (SCM) intake and the pleasure-attenuated startle response (PAS), could be induced by an electric foot-shock stress challenge in group-housed rats. After foot-shock stress, reduced SCM intake was observed in cLH rats compared to non-helpless (cNLH) rats. Furthermore, cLH rats also showed a decreased PAS, indicating deficient reward perception. In summary, we demonstrate that a predisposition for learned helplessness interacts with stress to trigger anhedonic-like behaviour in cLH rats. These findings further add to the validity of congenitally learned helplessness as an animal model of depression, since gene-environment interactions are considered to play a role in the etiology of this disorder.

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

Science.gov (United States)

Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

2012-10-01

Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

Science.gov (United States)

Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

2017-08-01

Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Host stress and immune responses during aerosol challenge of Brown Norway rats with Yersinia pestis

Directory of Open Access Journals (Sweden)

Susan T Gater

2012-11-01

Full Text Available Inhalation exposure models are becoming the preferred method for the comparative study of respiratory infectious diseases due to their resemblance to the natural route of infection. To enable precise delivery of pathogen to the lower respiratory tract in a manner that imposes minimal biosafety risk, nose-only exposure systems have been developed. Early inhalation exposure technology for infectious disease research grew out of technology used in asthma research where predominantly the Collison nebulizer is used to generate an aerosol by beating a liquid sample against glass. Although infectious aerosol droplets of 1-5µm in size can be generated, the Collison often causes loss of viability. In this work, we evaluate a gentler method for aerosolization of living cells and describe the use of the Sparging Liquid Aerosol Generator (SLAG in a rat pneumonic plague model. The SLAG creates aerosols by continuous dripping of liquid sample on a porous metal disc. We show the generation of 0.5 to 1µm Y. pestis aerosol particles using the SLAG with spray factors typically ranging from 10-7 to 10-8 with no detectable loss of bacterial viability. Delivery of these infectious particles via nose-only exposure led to the rapid development of lethal pneumonic plague. Further, we evaluated the effect of restraint-stress imposed by the nose-only exposure chamber on early inflammatory responses and bacterial deposition. Elevated serum corticosterone which peaked at 2 hrs post-procedure indicated the animals experienced stress as a result of restraint in the nose-only chamber. However, we observed no correlation between elevated corticosterone and the amount of bacterial deposition or inflammation in the lungs. Together these data demonstrate the utility of the SLAG and the nose-only chamber for aerosol challenge of rodents by Y. pestis.

Fabrication of a small animal restraint for synchrotron biomedical imaging using a rapid prototyper

International Nuclear Information System (INIS)

Zhu Ying; Zhang Honglin; McCrea, Richard; Bewer, Brian; Wiebe, Sheldon; Nichol, Helen; Ryan, Christopher; Wysokinski, Tomasz; Chapman, Dean

2007-01-01

Biomedical research at synchrotron facilities may involve imaging live animals that must remain motionless for extended periods of time to obtain quality images. Even breathing movements reduce image quality but on the other hand excessive restraint of animals increases morbidity and mortality. We describe a humane animal restraint designed to eliminate head movements while promoting animal survival. This paper describes how an animal restraint that conforms to the shape of an animal's head was fabricated by a 3D prototyper. The method used to translate medical computed tomography (CT) data to a 3D stereolithography format is described and images of its use at the Canadian Light Source (CLS) are shown. This type of restraint holds great promise in improving image quality and repeatability while reducing stress on experimental animals

PDBStat: a universal restraint converter and restraint analysis software package for protein NMR

International Nuclear Information System (INIS)

Tejero, Roberto; Snyder, David; Mao, Binchen; Aramini, James M.; Montelione, Gaetano T.

2013-01-01

The heterogeneous array of software tools used in the process of protein NMR structure determination presents organizational challenges in the structure determination and validation processes, and creates a learning curve that limits the broader use of protein NMR in biology. These challenges, including accurate use of data in different data formats required by software carrying out similar tasks, continue to confound the efforts of novices and experts alike. These important issues need to be addressed robustly in order to standardize protein NMR structure determination and validation. PDBStat is a C/C++ computer program originally developed as a universal coordinate and protein NMR restraint converter. Its primary function is to provide a user-friendly tool for interconverting between protein coordinate and protein NMR restraint data formats. It also provides an integrated set of computational methods for protein NMR restraint analysis and structure quality assessment, relabeling of prochiral atoms with correct IUPAC names, as well as multiple methods for analysis of the consistency of atomic positions indicated by their convergence across a protein NMR ensemble. In this paper we provide a detailed description of the PDBStat software, and highlight some of its valuable computational capabilities. As an example, we demonstrate the use of the PDBStat restraint converter for restrained CS-Rosetta structure generation calculations, and compare the resulting protein NMR structure models with those generated from the same NMR restraint data using more traditional structure determination methods. These results demonstrate the value of a universal restraint converter in allowing the use of multiple structure generation methods with the same restraint data for consensus analysis of protein NMR structures and the underlying restraint data

PDBStat: a universal restraint converter and restraint analysis software package for protein NMR

Energy Technology Data Exchange (ETDEWEB)

Tejero, Roberto [Rutgers, The State University of New Jersey, Center for Advanced Biotechnology and Medicine (United States); Snyder, David [William Paterson University, Department of Chemistry (United States); Mao, Binchen; Aramini, James M.; Montelione, Gaetano T., E-mail: guy@cabm.rutgers.edu [Rutgers, The State University of New Jersey, Center for Advanced Biotechnology and Medicine (United States)

2013-08-15

The heterogeneous array of software tools used in the process of protein NMR structure determination presents organizational challenges in the structure determination and validation processes, and creates a learning curve that limits the broader use of protein NMR in biology. These challenges, including accurate use of data in different data formats required by software carrying out similar tasks, continue to confound the efforts of novices and experts alike. These important issues need to be addressed robustly in order to standardize protein NMR structure determination and validation. PDBStat is a C/C++ computer program originally developed as a universal coordinate and protein NMR restraint converter. Its primary function is to provide a user-friendly tool for interconverting between protein coordinate and protein NMR restraint data formats. It also provides an integrated set of computational methods for protein NMR restraint analysis and structure quality assessment, relabeling of prochiral atoms with correct IUPAC names, as well as multiple methods for analysis of the consistency of atomic positions indicated by their convergence across a protein NMR ensemble. In this paper we provide a detailed description of the PDBStat software, and highlight some of its valuable computational capabilities. As an example, we demonstrate the use of the PDBStat restraint converter for restrained CS-Rosetta structure generation calculations, and compare the resulting protein NMR structure models with those generated from the same NMR restraint data using more traditional structure determination methods. These results demonstrate the value of a universal restraint converter in allowing the use of multiple structure generation methods with the same restraint data for consensus analysis of protein NMR structures and the underlying restraint data.

The effect of stress on the acute neurotoxicity of the organophosphate insecticide chlorpyrifos

International Nuclear Information System (INIS)

Hancock, Sandra; Ehrich, Marion; Hinckley, Jonathan; Pung, Thitiya; Jortner, Bernard S.

2007-01-01

A study was conducted to determine if multiple exposures to several stress paradigms might affect the anticholinesterase effect of subsequently administered organophosphate insecticide chlorpyrifos. Male Sprague-Dawley rats were subject to daily periods of restraint, swimming, a combination of the two, or neither of the two (controls) (n = 8/group) for 5 days per week over a six-week period. The most profound stress, as measured by reduced body weight gain and elevated levels of plasma corticosterone, was swimming. On day 39 of the study, shortly after the daily stress episode, one half of the rats in each group was dosed with 60 mg/kg chlorpyrifos subcutaneously. This had no effect on subsequent levels of plasma corticosterone. There were no stress-related differences in the degree of chlorpyrifos-induced inhibition of brain acetylcholinesterase in animals sacrificed on day 43

125I-iomazenil-benzodiazepine receptor binding during psychological stress in rats

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Tsuchida, Daisuke; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

2002-01-01

We investigated the changes in 125 I-iomazenil ( 125 I-IMZ) benzodiazepine receptor (BZR) binding with psychological stress in a rat model. Six male Wistar rats were placed under psychological stress for 1 hour by using a communication box. No physical stress was not received. 1.85 MBq of 125 I-IMZ was injected into the lateral tail vein and the rat was killed 3 hours later. Twenty-micormeter-thick sections of the brain were collected and % injected dose per body weight (% ID/BW) of eleven regions (frontal, parietal, temporal, occipital cortices, caudate putamen, accumubens nuclei, globus pallidus, amygdala, thalamus, hippocampus and hypothalamus) were calculated by autoradiography. The %ID/BW of rats which were placed under psychological stress was compared with that of 6 control rats. The %ID/BW of rats which were placed under psychological stress diffusely tended to show a reduction in 125 I-IMZ-BZR binding. A significant decrease in BZR binding was observed in the hippocampus of the rats which were placed under psychological stress. 125 I-IMZ-BZR binding tended to decrease throughout the brain. (author)

Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway.

Science.gov (United States)

Jia, Ning; Sun, Qinru; Su, Qian; Dang, Shaokang; Chen, Guomin

2016-12-01

Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS) level，mitochondrial membrane potential (MMP), ATP and cytochrome c oxidase (CcO) activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2) and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt) and phosphorylation of CREB (pCREB), which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway. Therefore

Taurine promotes cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway

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Ning Jia

2016-12-01

Full Text Available Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS. Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS level，mitochondrial membrane potential (MMP, ATP and cytochrome c oxidase (CcO activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB-peroxisome proliferator-activated receptor–γ coactivator-1α (PGC1α pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2 and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt and phosphorylation of CREB (pCREB, which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1�

Lack of Social Support Raises Stress Vulnerability in Rats with a History of Ancestral Stress.

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Faraji, Jamshid; Soltanpour, Nabiollah; Lotfi, Hamid; Moeeini, Reza; Moharreri, Ali-Reza; Roudaki, Shabnam; Hosseini, S Abedin; Olson, David M; Abdollahi, Ali-Akbar; Soltanpour, Nasrin; Mohajerani, Majid H; Metz, Gerlinde A S

2017-07-13

Stress is a primary risk factor for psychiatric disorders. However, it is not fully understood why some stressed individuals are more vulnerable to psychiatric disorders than others. Here, we investigated whether multigenerational ancestral stress produces phenotypes that are sensitive to depression-like symptoms in rats. We also examined whether social isolation reveals potentially latent sensitivity to depression-like behaviours. F4 female rats born to a lineage of stressed mothers (F0-F3) received stress in adulthood while housed in pairs or alone. Social isolation during stress induced cognitive and psychomotor retardation only in rats exposed to ancestral stress. Social isolation also hampered the resilience of the hypothalamic-pituitary-adrenal axis to chronic stress and reduced hippocampal volume and brain-derived neurotrophic factor (BDNF) expression. Thus, synergy between social isolation and stress may unmask a latent history of ancestral stress, and raises vulnerability to mental health conditions. The findings support the notion that social support critically promotes stress coping and resilience.

Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral effects of acute and chronic restraint stress in male C57BL/6 mice.

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Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E

2015-01-01

Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following 7-day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice. However, longer periods of daily restraint (14-21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of ARS and short-term (7 days) CRS.

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

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Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

32 CFR 636.34 - Restraint systems.

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2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Restraint systems. 636.34 Section 636.34 National... Restraint systems. (a) Restraint systems (seat belts) will be worn by all operators and passengers of U.S. Government vehicles on or off the installations. (b) Restraint systems will be worn by all civilian personnel...

Protective effect of low dose caffeine on psychological stress and cognitive function.

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Çakır, Özgür Kasımay; Ellek, Nurfitnat; Salehin, Nabila; Hamamcı, Rabia; Keleş, Hülya; Kayalı, Damla Gökçeoğlu; Akakın, Dilek; Yüksel, Meral; Özbeyli, Dilek

2017-01-01

Caffeine is an adrenergic antagonist that enhances neuronal activity. Psychological stress depresses cognitive function. To investigate the effects of acute and chronic low dose caffeine on anxiety-like behavior and cognitive functions of acute or chronic psychological stressed rats. Acute or chronic caffeine (3mg/kg) was administered to male Sprague Dawley rats (200-250g, n=42) before acute (cat odor) and chronic variable psychological stress (restraint overcrowding stress, elevated plus maze, cat odor, forced swimming) induction. Anxiety and cognitive functions were evaluated by hole-board and object recognition tests. The brain glutathione and malondialdehyde assays, myeloperoxidase, nitric oxide (NO), superoxide dismutase (SOD), luminol and lucigenin activity and histological examination were done. ANOVA and Student's t-test were used for statistical analysis. The depressed cognitive function with chronic stress exposure and the increased anxiety-like behavior with both stress inductions were improved via both caffeine applications (pcaffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (pcaffeine (pcaffeine (pcaffeine decreased SOD activity (pcaffeine. The increased anxiety-like behavior and depleted cognitive functions under stress conditions were improved with both acute and predominantly chronic caffeine pretreatments by decreasing oxidative damage parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

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fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

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Salvadore Christopher

2004-09-01

Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.

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Ismael Palacios-García

Full Text Available Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that

Standardized Environmental Enrichment Supports Enhanced Brain Plasticity in Healthy Rats and Prevents Cognitive Impairment in Epileptic Rats

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Kouchi, Hayet Y.; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S.; Bezin, Laurent

2013-01-01

Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories. PMID:23342033

Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

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Raafat P Fares

Full Text Available Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage, which offers: (1 minimally stressful social interactions; (2 increased voluntary exercise; (3 multiple entertaining activities; (4 cognitive stimulation (maze exploration, and (5 novelty (maze configuration changed three times a week. The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.

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Terrill, Sarah J; Maske, Calyn B; Williams, Diana L

2018-03-03

Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 min of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4-6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats.

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Azman, Khairunnuur Fairuz; Zakaria, Rahimah; Abdul Aziz, Che Badariah; Othman, Zahiruddin

2016-01-01

Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

{sup 125}I-iomazenil-benzodiazepine receptor binding during psychological stress in rats

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Fukumitsu, Nobuyoshi; Tsuchida, Daisuke; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka [Jikei Univ., Tokyo (Japan). School of Medicine

2002-05-01

We investigated the changes in {sup 125}I-iomazenil ({sup 125}I-IMZ) benzodiazepine receptor (BZR) binding with psychological stress in a rat model. Six male Wistar rats were placed under psychological stress for 1 hour by using a communication box. No physical stress was not received. 1.85 MBq of {sup 125}I-IMZ was injected into the lateral tail vein and the rat was killed 3 hours later. Twenty-micormeter-thick sections of the brain were collected and % injected dose per body weight (% ID/BW) of eleven regions (frontal, parietal, temporal, occipital cortices, caudate putamen, accumubens nuclei, globus pallidus, amygdala, thalamus, hippocampus and hypothalamus) were calculated by autoradiography. The %ID/BW of rats which were placed under psychological stress was compared with that of 6 control rats. The %ID/BW of rats which were placed under psychological stress diffusely tended to show a reduction in {sup 125}I-IMZ-BZR binding. A significant decrease in BZR binding was observed in the hippocampus of the rats which were placed under psychological stress. {sup 125}I-IMZ-BZR binding tended to decrease throughout the brain. (author)

Predictors of restraint use among child occupants.

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Benedetti, Marco; Klinich, Kathleen D; Manary, Miriam A; Flannagan, Carol A

2017-11-17

The objective of this study was to identify factors that predict restraint use and optimal restraint use among children aged 0 to 13 years. The data set is a national sample of police-reported crashes for years 2010-2014 in which type of child restraint is recorded. The data set was supplemented with demographic census data linked by driver ZIP code, as well as a score for the state child restraint law during the year of the crash relative to best practice recommendations for protecting child occupants. Analysis used linear regression techniques. The main predictor of unrestrained child occupants was the presence of an unrestrained driver. Among restrained children, children had 1.66 (95% confidence interval, 1.27, 2.17) times higher odds of using the recommended type of restraint system if the state law at the time of the crash included requirements based on best practice recommendations. Children are more likely to ride in the recommended type of child restraint when their state's child restraint law includes wording that follows best practice recommendations for child occupant protection. However, state child restraint law requirements do not influence when caregivers fail to use an occupant restraint for their child passengers.

Presynaptic plasticity as a hallmark of rat stress susceptibility and antidepressant response.

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Jose Luis Nieto-Gonzalez

Full Text Available Two main questions are important for understanding and treating affective disorders: why are certain individuals susceptible or resilient to stress, and what are the features of treatment response and resistance? To address these questions, we used a chronic mild stress (CMS rat model of depression. When exposed to stress, a fraction of rats develops anhedonic-like behavior, a core symptom of major depression, while another subgroup of rats is resilient to CMS. Furthermore, the anhedonic-like state is reversed in about half the animals in response to chronic escitalopram treatment (responders, while the remaining animals are resistant (non-responder animals. Electrophysiology in hippocampal brain slices was used to identify a synaptic hallmark characterizing these groups of animals. Presynaptic properties were investigated at GABAergic synapses onto single dentate gyrus granule cells. Stress-susceptible rats displayed a reduced probability of GABA release judged by an altered paired-pulse ratio of evoked inhibitory postsynaptic currents (IPSCs (1.48 ± 0.25 compared with control (0.81 ± 0.05 and stress-resilient rats (0.78 ± 0.03. Spontaneous IPSCs (sIPSCs occurred less frequently in stress-susceptible rats compared with control and resilient rats. Finally, a subset of stress-susceptible rats responding to selective serotonin reuptake inhibitor (SSRI treatment showed a normalization of the paired-pulse ratio (0.73 ± 0.06 whereas non-responder rats showed no normalization (1.2 ± 0.2. No changes in the number of parvalbumin-positive interneurons were observed. Thus, we provide evidence for a distinct GABAergic synaptopathy which associates closely with stress-susceptibility and treatment-resistance in an animal model of depression.

Social stress contagion in rats: Behavioural, autonomic and neuroendocrine correlates.

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Carnevali, Luca; Montano, Nicola; Statello, Rosario; Coudé, Gino; Vacondio, Federica; Rivara, Silvia; Ferrari, Pier Francesco; Sgoifo, Andrea

2017-08-01

The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between

Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

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Zhou, Yuan-Yuan; Wanner, Natalie J; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing-Hong; Gu, Jian-Guo; Xu, Guang-Yin

2012-01-01

AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P

Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic

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Bourke, Chase H.; Neigh, Gretchen N.

2011-01-01

Evidence suggests that women are more susceptible to stress-related disorders than men. Animal studies demonstrate a similar female sensitivity to stress and have been used to examine the underlying neurobiology of sex-specific effects of stress. Although our understanding of the sex-specific effects of chronic adolescent stress has grown in recent years, few studies have reported the effects of adolescent stress on depressive-like behavior. The purpose of this study was to determine if a chronic mixed modality stressor (consisting of isolation, restraint, and social defeat) during adolescence (PND37-49) resulted in differential and sustained changes in depressive-like behavior in male and female Wistar rats. Female rats exposed to chronic adolescent stress displayed decreased sucrose consumption, hyperactivity in the elevated plus maze, decreased activity in the forced swim test, and a blunted corticosterone response to an acute forced swim stress compared to controls during both adolescence (PND48-57) and adulthood (PND96-104). Male rats exposed to chronic adolescent stress did not manifest significant behavioral changes at either the end of adolescence or in adulthood. These data support the proposition that adolescence may be a stress sensitive period for females and exposure to stress during adolescence results in behavioral effects that persist in females. Studies investigating the sex-specific effects of chronic adolescent stress may lead to a better understanding of the sexually dimorphic incidence of depressive and anxiety disorders in humans and ultimately improve prevention and treatment strategies. PMID:21466807

Chronic stress does not impair liver regeneration in rats

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Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove

2015-01-01

a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

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Abush, Hila; Akirav, Irit

2013-07-01

Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

The role of galanin system in modulating depression, anxiety, and addiction-like behaviors after chronic restraint stress.

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Zhao, X; Seese, R R; Yun, K; Peng, T; Wang, Z

2013-08-29

There is high comorbidity between stress-related psychiatric disorders and addiction, suggesting they may share one or more common neurobiological mechanisms. Because of its role in both depressive and addictive behaviors, the galanin system is a strong candidate for such a mechanism. In this study, we tested if galanin and its receptors are involved in stress-associated behaviors and drug addiction. Mice were exposed to 21 days of chronic restraint stress (CRS); subsequently, mRNA levels of galanin, galanin receptors (GalRs), the rate-limiting enzymes for the synthesis of monoamines, and monoamine autoreceptors were measured in the nucleus accumbens by a quantitative real-time polymerase chain reaction. Moreover, we tested the effects of this stress on morphine-induced addictive behaviors. We found that CRS induced anxiety and depression-like behaviors, impaired the formation and facilitated the extinction process in morphine-induced conditioned place preference (CPP), and also blocked morphine-induced behavioral sensitization. These behavioral results were accompanied by a CRS-dependent increase in the mRNA expression of galanin, GalR1, tyrosine hydroxylase (TH), tryptophan hydroxylase 2, and 5-HT1B receptor. Interestingly, treatment with a commonly used antidepressant, fluoxetine, normalized the CRS-induced behavioral changes based on reversing the higher expression of galanin and TH while increasing the expression of GalR2 and α2A-adrenceptor. These results indicate that activating the galanin system, with corresponding changes to noradrenergic systems, following chronic stress may modulate stress-associated behaviors and opiate addiction. Our findings suggest that galanin and GalRs are worthy of further exploration as potential therapeutic targets to treat stress-related disorders and drug addiction. Copyright © 2013 IBRO. All rights reserved.

Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

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Alvarez, Pedro; Green, Paul G; Levine, Jon D

2018-06-01

Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Anti-oxidative effects of Rooibos tea (Aspalathus linearis on immobilization-induced oxidative stress in rat brain.

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In-Sun Hong

Full Text Available Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea's ability to (i reverse the increase in stress-related metabolites (5-HIAA and FFA, (ii prevent lipid peroxidation (LPO, (iii restore stress-induced protein degradation (PD, (iv regulate glutathione metabolism (GSH and GSH/GSSG ratio, and (v modulate changes in the activities of antioxidant enzymes (SOD and CAT.

Restraint methods for radiography in dogs and cats

International Nuclear Information System (INIS)

Scrivani, P.V.; Bednarski, R.M.; Myer, C.W.; Dykes, N.L.

1996-01-01

Excellent patient restraint techniques are necessary to produce high-quality diagnostic images during survey and contrast radiography and ultrasonography. Use of non manual physical restraint (i.e., devices to hold the patient in position) helps reduce the exposure of veterinary personnel to radiation. Exposure of personnel to radiation should be kept as low as reasonably achievable. Usually, this involves taking the radiograph when no personnel are present in the room. Some procedures, however, require the presence of the veterinarian. No personnel should ever put any part of their bodies in the path of the x-ray beam. Protective gear must be worn. Physical restraint can be facilitated by chemical restraint, which varies from minimal sedation to general anesthesia. Appropriate chemical restraint for radiography is the minimum amount of sedation required for the efficient and safe completion of the radiographic examination. Chemical restraint techniques vary according to the patient's physical status, the type of examination, and the skill of the examiner in non manual restraint techniques. This article describes techniques for non manual restraint and protocols for chemical restraint for dogs and cats

Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

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Sara Peñasco

2015-01-01

Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

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Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

The effects of propolis extract on ovarian tissue and oxidative stress in rats with maternal separation stress

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Atefeh Arabameri

2017-09-01

Full Text Available Abstract Background: Stress in infancy has dramatic effects on different systems, including the nervous system, endocrine, immune, reproductive and etc. Objective: The purpose of this study was to investigate the effects of extract of Iranian propolis (EIP on ovarian tissue and oxidative stress in rats with maternal separation stress. Materials and Methods: 48 immature female rats were divided randomly into six groups. 1 Control group, 2 Control group+saline, 3 Stress group, includes infants that were separated from their mothers 6 hr/day, the 4th, 5th and 6th groups consisted of infants who in addition to daily stress received 50, 100 and 200 mg/kg of EIP, respectively. Then serum corticosterone, 17-beta-estradiol, malondialdehyde, total superoxide dismutase, glutathione peroxidase and ferric reducing antioxidant power levels were measured. The ovarian sections were stained by H&E, PAS, and TUNEL methods and were studied with optical microscopy. Results: Stress increased the blood serum corticosterone levels and 17-beta-estradiol reduced significantly (p<0.001 and EIP prevented from this changes (p<0.01. EIP significantly increased the number of ovarian follicles, oocytes and oocytes diameter in neonatal rat following stress (p<0.01. EIP also significantly decreased the number of atretic follicles, TUNEL+granulosa cells, malondialdehyde levels and increased ferric reducing antioxidant power, total superoxide dismutase and glutathione peroxidase serum levels in neonatal rats following stress. The dose of 200 mg/kg EIP was more effective. Conclusion: This Study showed that the Iranian Propolis significantly could prevent oxidative stress and histopathological changes in the ovary of the neonatal rat the following stress.

Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.

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Gass, N; Becker, R; Schwarz, A J; Weber-Fahr, W; Clemm von Hohenberg, C; Vollmayr, B; Sartorius, A

2016-12-06

Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.

A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

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Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

2014-04-10

In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval impairment in rats.

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Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba; Zarrindast, Mohammad-Reza

2014-04-01

The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment.

Palatable food avoidance and acceptance learning with different stressors in female rats.

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Liang, N-C; Smith, M E; Moran, T H

2013-04-03

Stress activates the hypothalamus-pituitary-adrenal (HPA) axis leading to the release of glucocorticoids (GC). Increased activity of the HPA axis and GC exposure has been suggested to facilitate the development of obesity and metabolic syndrome. Nonetheless, different stressors can produce distinct effects on food intake and may support different directions of food learning e.g. avoidance or acceptance. This study examined whether interoceptive (LiCl and exendin-4) and restraint stress (RS) support similar or distinct food learning. Female rats were exposed to different stressors after their consumption of a palatable food (butter icing). After four palatable food-stress pairings, distinct intakes of the butter icing were observed in rats treated with different stressors. Rats that received butter icing followed by intraperitoneal injections of LiCl (42.3mg/kg) and exendin-4 (10μg/kg) completely avoided the palatable food with subsequent presentations. In contrast, rats experiencing RS paired with the palatable food increased their consumption of butter icing across trials and did so to a greater degree than rats receiving saline injections. These data indicate that interoceptive and psychosocial stressors support conditioned food avoidance and acceptance, respectively. Examination of c-Fos immunoreactivity revealed distinct neural activation by interoceptive and psychosocial stressors that could provide the neural basis underlying opposite direction of food acceptance learning. Published by Elsevier Ltd.

Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

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Zipeng Gong

2014-01-01

Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

OpenAIRE

Breese, George R; Knapp, Darin J; Overstreet, David H

2004-01-01

Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposur...

Functional β2-adrenoceptors in rat left atria: effect of foot-shock stress.

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Moura, André Luiz de; Hyslop, Stephen; Grassi-Kassisse, Dora M; Spadari, Regina C

2017-09-01

Altered sensitivity to the chronotropic effect of catecholamines and a reduction in the β 1 /β 2 -adrenoceptor ratio have previously been reported in right atria of stressed rats, human failing heart, and aging. In this report, we investigated whether left atrial inotropism was affected by foot-shock stress. Male rats were submitted to 3 foot-shock sessions and the left atrial inotropic response, adenylyl cyclase activity, and β-adrenoceptor expression were investigated. Left atria of stressed rats were supersensitive to isoprenaline when compared with control rats and this effect was abolished by ICI118,551, a selective β 2 -receptor antagonist. Schild plot slopes for the antagonism between CGP20712A (a selective β 1 -receptor antagonist) and isoprenaline differed from unity in atria of stressed but not control rats. Atrial sensitivity to norepinephrine, as well as basal and forskolin- or isoprenaline-stimulated adenylyl cyclase activities were not altered by stress. The effect of isoprenaline on adenylyl cyclase stimulation was partially blocked by ICI118,551 in atrial membranes of stressed rats. These findings indicate that foot-shock stress equally affects inotropism and chronotropism and that β 2 -adrenoceptor upregulation contributes to the enhanced inotropic response to isoprenaline.

Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats

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Anibal Pacheco

2017-08-01

Full Text Available Previous studies in rats have demonstrated that chronic restraint stress triggers anhedonia, depressive-like behaviors, anxiety and a reduction in dendritic spine density in hippocampal neurons. In this study, we compared the effect of repeated stress on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA and N-methyl-D-aspartate (NMDA receptor subunits in dorsal and ventral hippocampus (VH. Adult male Sprague-Dawley rats were randomly divided into control and stressed groups, and were daily restrained in their motion (2.5 h/day during 14 days. We found that chronic stress promotes an increase in c-Fos mRNA levels in both hippocampal areas, although it was observed a reduction in the immunoreactivity at pyramidal cell layer. Furthermore, Arc mRNAs levels were increased in both dorsal and VH, accompanied by an increase in Arc immunoreactivity in dendritic hippocampal layers. Furthermore, stress triggered a reduction in PSD-95 and NR1 protein levels in whole extract of dorsal and VH. Moreover, a reduction in NR2A/NR2B ratio was observed only in dorsal pole. In synaptosomal fractions, we detected a rise in NR1 in dorsal hippocampus (DH. By indirect immunofluorescence we found that NR1 subunits rise, especially in neuropil areas of dorsal, but not VH. In relation to AMPA receptor (AMPAR subunits, chronic stress did not trigger any change, either in dorsal or ventral hippocampal areas. These data suggest that DH is more sensitive than VH to chronic stress exposure, mainly altering the expression of NMDA receptor (NMDAR subunits, and probably favors changes in the configuration of this receptor that may influence the function of this area.

Dobutamine stress echocardiography in healthy adult male rats

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Couet Jacques

2005-10-01

Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

B-type natriuretic peptide (BNP serum levels in rats after forced repeated swimming stress

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Almira Hadžovic-Džuvo

2011-02-01

Full Text Available Aim To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Methods Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n =8 and stress group (n =8. Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep containing tap water (temperature ca. 25°C. The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the irst day to 40 minutes on days 6 and 7. Rats were sacriiced and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.. Results There was no statistically signiicant difference between mean BNP serum level in the stress group after the swimming period (0.81±0.14 ng/ml as compared to the unstressed group of rats (0.8 ±0.08ng/ml. After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs.272.8 g, but this difference was not statistically signiicant. The stress period had no inluence on food intake in the stress rat group. Conclusion The workload consisting of 40-minutes long swimming session is not suficient to provoke BNP release from myocardium in rats.

B-type natriuretic peptide (BNP) serum levels in rats after forced repeated swimming stress.

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Hadzovic-Dzuvo, Almira; Valjevac, Amina; Avdagić, Nesina; Lepara, Orhan; Zaćiragić, Asija; Jadrić, Radivoj; Alajbegović, Jasmin; Prnjavorac, Besim

2011-02-01

To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n = 8) and stress group (n = 8). Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep) containing tap water (temperature ca. 25 degrees C). The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the first day to 40 minutes on days 6 and 7. Rats were sacrificed and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.). There was no statistically significant difference between mean BNP serum level in the stress group after the swimming period (0.81 +/- 0.14 ng/ml) as compared to the unstressed group of rats (0.8 +/- 0.08 ng/ml). After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs. 272.8 g), but this difference was not statistically significant. The stress period had no influence on food intake in the stress rat group. The workload consisting of 40-minutes long swimming session is not sufficient to provoke BNP release from myocardium in rats.

Efeitos do estresse agudo de contenção, do estresse crônico de natação e da administração de glutamina sobre a liberação de superóxido por macrófagos alveolares de ratos Effects of acute restraint stress, chronic swim stress and glutamine administration on the release of superoxide from alveolar macrophages of rats

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Elizabeth do Nascimento

2007-08-01

Full Text Available OBJETIVO: Avaliar a liberação de ânion superóxido por macrófagos alveolares em ratos submetidos ou não ao estresse agudo, ao exercício físico de natação e à suplementação com glutamina. MÉTODOS: Quarenta e dois ratos machos da linhagem Wistar com idade em torno de 62 (desvio-padrão=3 dias de idade foram divididos em grupos controle, treino, estresse e glutamina. Após a intervenção, macrófagos alveolares foram coletados e estimulados com acetato de formol miristato para a avaliação da liberação de ânion superóxido. RESULTADOS: Em comparação à primeira hora (controle=26,2, desvio-padrão=4,2; treino=28,7, desvio-padrão=5,1; estresse=20,3, desvio-padrão=4,4; glutamina=26,2, desvio-padrão=4,2, houve aumento (pOBJECTIVE: To assess the release of superoxide anion from alveolar macrophages of rats submitted or not to acute restraint stress, forced swimming and glutamine supplementation. METHODS: Forty-two male Wistar rats aging roughly 62 days (standard deviation=3 were randomly divided into four groups: control, training, stress and glutamine. After the intervention, alveolar macrophages were collected and stimulated with phorbol myristate acetate to assess the release of superoxide anion. RESULTS: When compared with the first hour (control=26.2, standard deviation=4.2; training=28.7, standard deviation=5.1; stress=20.3 , standard deviation=4.4; glutamine=26.2, standard deviation=4.2, the release of superoxide increased (p<0.001 in all experimental groups in the second hour (control=38.4, standard deviation=4.9; training=40.7, standard deviation=6.1; stress=30.2, standard deviation=5.6; glutamine=39.2, standard deviation=5.2 of observation. Training and glutamine supplementation did not induce differences in the release of superoxide from alveolar macrophages when compared with the control group. Only the rats submitted to stress showed a reduction in the release of superoxide in both the first (20.3, standard deviation

Developmental differences in stress responding after repeated underwater trauma exposures in rats.

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Altman, Daniel E; Simmons, Laurence P; Vuong, Chau T; Taylor, Rachel M; Sousa, Jason C; Marcsisin, Sean R; Zottig, Victor E; Moore, Nicole L T

2018-05-01

Adolescence is a distinct developmental period characterized by behavioral and physiological maturation. Rapid ongoing changes during neurodevelopment in particular present potential opportunities for stress to have lasting effects on longitudinal outcomes of behavioral and neuroendocrine function. While adult stress effects on outcomes during adulthood have been characterized, little is known about the lasting effects of adolescent repeated stressor exposure on outcomes during adolescence. We have previously reported different stress responses in adolescent rats relative to adult rats, including a blunted fear response outcome in adulthood in rats stressed during adolescence. The present study characterized the ontogeny of behavioral and neuroendocrine responses to eight underwater trauma (UWT) exposures in rats over a two week poststress time period during adolescence (P34) or adulthood (P83) relative to age-matched control groups that underwent eight swimming episodes without UWT. Repeated UWT exposures starting in adolescence, but not adulthood, resulted in adverse behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone responses did not differ between UWT-exposed and controls for either age group at 1 day or at 7 days poststress, although there was an effect of age on corticosterone levels. We conclude that repeated UWT stress events have a lasting, negative behavioral effect on adolescent rats that is not observed in adult rats after the two-week exposure window. These results suggest that neurophysiological mechanisms underlying recovery from a repeated stressor are immature in adolescence relative to adulthood in rats.

Effects of Exercise Training and Social Environment on Stress Resilience in Male and Female Long-Evans Rats

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2010-03-15

Dalla et al., 2005; Marin, Cruz, & Planeta , 2007; Mineur, Belzung, & Crusio, 2006; Padilla et al., 2009; Pohl et al., 2007; Slawecki, 2005...48. 156 Marin, M.T., Cruz, F.C., & Planeta , C.S. (2007). Chronic restraint or variable stresses differently affect the behavior, corticosterone

Diffusion-weighted MRI and quantitative biophysical modeling of hippocampal neurite loss in chronic stress.

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Peter Vestergaard-Poulsen

Full Text Available Chronic stress has detrimental effects on physiology, learning and memory and is involved in the development of anxiety and depressive disorders. Besides changes in synaptic formation and neurogenesis, chronic stress also induces dendritic remodeling in the hippocampus, amygdala and the prefrontal cortex. Investigations of dendritic remodeling during development and treatment of stress are currently limited by the invasive nature of histological and stereological methods. Here we show that high field diffusion-weighted MRI combined with quantitative biophysical modeling of the hippocampal dendritic loss in 21 day restraint stressed rats highly correlates with former histological findings. Our study strongly indicates that diffusion-weighted MRI is sensitive to regional dendritic loss and thus a promising candidate for non-invasive studies of dendritic plasticity in chronic stress and stress-related disorders.

Oxidative stress of crystalline lens in rat menopausal model

OpenAIRE

Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

2016-01-01

ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Gro...

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats.

Science.gov (United States)

Abbas, Ghulam; Naqvi, Sabira; Mehmood, Shahab; Kabir, Nurul; Dar, Ahsana

2011-10-01

The current study was aimed to investigate the correlations between immobility time in the forced swimming test (FST, a behavioral indicator of stress level) and hippocampal monoamine levels (markers of depression), plasma adrenalin level (a peripheral marker of stress) as well as fluoro-jade C staining (a marker of neurodegeneration). Male Sprague-Dawley rats were subjected to acute, sub-chronic (7 d) or chronic (14 d) FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment (3 mg/kg subcutaneously for 4 d) were stained with fluoro-jade C. The rats subjected to swimming stress (acute, sub-chronic and chronic) showed long immobility times [(214 +/- 5), (220 +/- 4) and (231 +/- 7) s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fluoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. The immobility time in the FST does not correlate with markers of depression (monoamine levels) and internal stress (adrenalin levels and neurodegeneration), hence this parameter may not be a true indicator of stress level.

Oxidative stress of crystalline lens in rat menopausal model.

Science.gov (United States)

Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

2016-01-01

To evaluate lenticular oxidative stress in rat menopausal models. Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Group 3), and the remaining 10 rats were administered intraperitoneal streptozocin to induce diabetes mellitus (Group 4). Total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurements of the crystalline lenses were analyzed. The mean OSI was the lowest in group 1 and highest in group 4. Nevertheless, the difference between the groups was not statistically significant in terms of OSI (p >0.05). The mean TOS values were similar between the groups (p >0.05), whereas the mean TAC of group 1 was significantly higher than that of the other groups (p <0.001). Our results indicate that menopause may not promote cataract formation.

Restraint Use in Older Adults Receiving Home Care.

Science.gov (United States)

Scheepmans, Kristien; Dierckx de Casterlé, Bernadette; Paquay, Louis; Van Gansbeke, Hendrik; Milisen, Koen

2017-08-01

To determine the prevalence, types, frequency, and duration of restraint use in older adults receiving home nursing care and to determine factors involved in the decision-making process for restraint use and application. Cross-sectional survey of restraint use in older adults receiving home care completed by primary care nurses. Homes of older adults receiving care from a home nursing organization in Belgium. Randomized sample of older adults receiving home care (N = 6,397; mean age 80.6; 66.8% female). For each participant, nurses completed an investigator-constructed and -validated questionnaire collecting information demographic, clinical, and behavioral characteristics and aspects of restraint use. A broad definition of restraint was used that includes a range of restrictive actions. Restraints were used in 24.7% of the participants, mostly on a daily basis (85%) and often for a long period (54.5%, 24 h/d). The most common reason for restraint use was safety (50.2%). Other reasons were that the individual wanted to remain at home longer, which necessitated the use of restraints (18.2%) and to provide respite for the informal caregiver (8.6%). The latter played an important role in the decision and application process. The physician was less involved in the process. In 64.5% of cases, there was no evaluation after restraint use was initiated. Use of restraints is common in older adults receiving home care nursing in Belgium. These results contribute to a better understanding of the complexity of use of restraints in home care, a situation that may be even more complex than in nursing homes and acute hospital settings. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Effect of housing rats within a pyramid on stress parameters.

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Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

2003-11-01

The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.

Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

Science.gov (United States)

Ortolani, Daniela; Garcia, Márcia Carvalho; Melo-Thomas, Liana; Spadari-Bratfisch, Regina Celia

2014-05-01

The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

Measurement of Dietary Restraint: Validity Tests of Four Questionnaires

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Williamson, Donald A.; Martin, Corby K.; York-Crowe, Emily; Anton, Stephen D.; Redman, Leanne M.; Han, Hongmei; Ravussin, Eric

2007-01-01

This study tested the validity of four measures of dietary restraint: Dutch Eating Behavior Questionnaire, Eating Inventory (EI), Revised Restraint Scale (RS), and the Current Dieting Questionnaire. Dietary restraint has been implicated as a determinant of overeating and binge eating. Conflicting findings have been attributed to different methods for measuring dietary restraint. The validity of four self-report measures of dietary restraint and dieting behavior was tested using: 1) factor analysis, 2) changes in dietary restraint in a randomized controlled trial of different methods to achieve calorie restriction, and 3) correlation of changes in dietary restraint with an objective measure of energy balance, calculated from the changes in fat mass and fat-free mass over a six-month dietary intervention. Scores from all four questionnaires, measured at baseline, formed a dietary restraint factor, but the RS also loaded on a binge eating factor. Based on change scores, the EI Restraint scale was the only measure that correlated significantly with energy balance expressed as a percentage of energy require d for weight maintenance. These findings suggest that that, of the four questionnaires tested, the EI Restraint scale was the most valid measure of the intent to diet and actual caloric restriction. PMID:17101191

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Science.gov (United States)

Belkina, L M; Popkova, E V; Lakomkin, V L; Kirillina, T N; Zhukova, A G; Sazontova, T G; Usacheva, M A; Kapel'ko, V I

2006-02-01

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.

International Space Station Crew Restraint Design

Science.gov (United States)

Whitmore, M.; Norris, L.; Holden, K.

2005-01-01

With permanent human presence onboard the International Space Station (ISS), crews will be living and working in microgravity, dealing with the challenges of a weightless environment. In addition, the confined nature of the spacecraft environment results in ergonomic challenges such as limited visibility and access to the activity areas, as well as prolonged periods of unnatural postures. Without optimum restraints, crewmembers may be handicapped for performing some of the on-orbit tasks. Currently, many of the tasks on ISS are performed with the crew restrained merely by hooking their arms or toes around handrails to steady themselves. This is adequate for some tasks, but not all. There have been some reports of discomfort/calluses on the top of the toes. In addition, this type of restraint is simply insufficient for tasks that require a large degree of stability. Glovebox design is a good example of a confined workstation concept requiring stability for successful use. They are widely used in industry, university, and government laboratories, as well as in the space environment, and are known to cause postural limitations and visual restrictions. Although there are numerous guidelines pertaining to ventilation, seals, and glove attachment, most of the data have been gathered in a 1-g environment, or are from studies that were conducted prior to the early 1980 s. Little is known about how best to restrain a crewmember using a glovebox in microgravity. In 2004, The Usability Testing and Analysis Facility (UTAF) at the NASA Johnson Space Center completed development/evaluation of several design concepts for crew restraints to meet the various needs outlined above. Restraints were designed for general purpose use, for teleoperation (Robonaut) and for use with the Life Sciences Glovebox. All design efforts followed a human factors engineering design lifecycle, beginning with identification of requirements followed by an iterative prototype/test cycle. Anthropometric

REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

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Nirupama R.

2010-09-01

Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

The effect of L-Arginine on the brain tissue of stressed rats

Directory of Open Access Journals (Sweden)

Batoul Ebadi

2010-01-01

Full Text Available   Abstract  Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

Active coping with stress suppresses glucose metabolism in the rat hypothalamus.

Science.gov (United States)

Ono, Yumie; Lin, Hsiao-Chun; Tzen, Kai-Yuan; Chen, Hui-Hsing; Yang, Pai-Feng; Lai, Wen-Sung; Chen, Jyh-Horng; Onozuka, Minoru; Yen, Chen-Tung

2012-03-01

We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

Supporting system for the core restraint of nuclear reactors

International Nuclear Information System (INIS)

Kaser, A.

1973-01-01

The core restraint of water cooled nuclear reactors which is needed to direct the flow of the coolant through the core can be manufactured only in a moderate wall thickness. Thus, the majority of the loads have to be transmitted to the core barrel which is more rigid. The patent refers to a system of circumferential and vertical support members most of which are free to move relatively to each other, thus reducing thermal stresses during operation. (P.K.)

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

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Lu-jing Chen

2014-01-01

Full Text Available Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood.

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

Science.gov (United States)

Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

2014-01-01

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

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Pietrelli, A; Di Nardo, M; Masucci, A; Brusco, A; Basso, N; Matkovic, L

2018-04-15

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats.

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Kudwa, Andrea E; McGivern, Robert F; Handa, Robert J

2014-04-22

The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor β (ERβ) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ERβ is co-expressed with oxytocin (OT) in neurons of the PVN, an ERβ-selective agonist was utilized to test the whether ERβ decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ERβ reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)(2), Thr(4)] OVT) or VEH, 20min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ERβ and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxidative stress of crystalline lens in rat menopausal model

Directory of Open Access Journals (Sweden)

Semra Acer

Full Text Available ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1. From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2, 10 were administered a daily injection of methylprednisolone until the end of the study (Group 3, and the remaining 10 rats were administered intraperitoneal streptozocin to induce diabetes mellitus (Group 4. Total oxidant status (TOS, total antioxidant capacity (TAC, and oxidative stress index (OSI measurements of the crystalline lenses were analyzed. Results: The mean OSI was the lowest in group 1 and highest in group 4. Nevertheless, the difference between the groups was not statistically significant in terms of OSI (p >0.05. The mean TOS values were similar between the groups (p >0.05, whereas the mean TAC of group 1 was significantly higher than that of the other groups (p <0.001. Conclusions: Our results indicate that menopause may not promote cataract formation.

Restraint, tendency toward overeating and ice cream consumption

NARCIS (Netherlands)

Van Strien, T; Cleven, A.H.G.; Schippers, G.

2000-01-01

OBJECTIVE: The examination of the prediction of grams of ice cream eaten by preload, restraint, susceptibility toward overeating, and interaction terms. METHOD: A milkshake-ice cream study on 200 females using the Restraint Scale (RS) and the restraint and disinhibition scales from the Three-Factor

Prenatal stress may increase vulnerability to life events comparison with the effects of prenatal dexamethasone

DEFF Research Database (Denmark)

Hougaard, Karin; Andersen, Maibritt B; Kjaer, Sanna L

2005-01-01

naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring......Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...... of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very...

A gene-environment study of cytoglobin in the human and rat hippocampus

DEFF Research Database (Denmark)

Hundahl, Christian Ansgar; Elfving, Betina; Müller, Heidi Kaastrup

2013-01-01

Cytoglobin (Cygb) was discovered a decade ago as the fourth vertebrate heme-globin. The function of Cygb is still unknown, but accumulating evidence from in vitro studies point to a putative role in scavenging of reactive oxygen species and nitric oxide metabolism and in vivo studies have shown C......NOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression.......Cytoglobin (Cygb) was discovered a decade ago as the fourth vertebrate heme-globin. The function of Cygb is still unknown, but accumulating evidence from in vitro studies point to a putative role in scavenging of reactive oxygen species and nitric oxide metabolism and in vivo studies have shown...... Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (n...

Oxidative stress in rats experimentally infected by Sporothrix schenckii.

Science.gov (United States)

Castro, Verônica S P; Da Silva, Aleksandro S; Thomé, Gustavo R; Wolkmer, Patrícia; Castro, Jorge L C; Costa, Márcio M; Graça, Dominguita L; Oliveira, Daniele C; Alves, Sydney H; Schetinger, Maria R C; Lopes, Sonia T A; Stefani, Lenita M; Azevedo, Maria I; Baldissera, Matheus D; Andrade, Cinthia M

2017-06-01

The aim of this study was to evaluate whether oxidative stress occurs in rats experimentally infected by Sporothrix schenckii, and its possible effect on disease pathogenesis. Thirty rats were divided into two groups: the group A (uninfected, n = 18) and the group B (infected by S. schenckii, n=21). Blood samples were collected on days 15, 30 and 40 post-infection (PI). At each sampling time, six rats of the group A, and seven of the group B were bled. TBARS (thiobarbituric acid reactive substances) levels in serum samples were measured to evaluate lipid peroxidation. In addition, catalase (CAT) and superoxide dismutase (SOD) activities, known as biomarkers of antioxidants levels, were verified in whole blood. Seric pro-inflammatory cytokine levels were measured (IFN-γ, TNF-α, and IL-6), which showed that these inflammatory mediators were at higher levels in the infected rats (P sporotrichosis showed significantly higher (p sporotrichosis is a likely mechanism for redox imbalance, and consequently cause the oxidative stress in experimentally infected rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time adjustment of ventricular restraint therapy in heart failure.

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Ghanta, Ravi K; Lee, Lawrence S; Umakanthan, Ramanan; Laurence, Rita G; Fox, John A; Bolman, Ralph Morton; Cohn, Lawrence H; Chen, Frederick Y

2008-12-01

Current ventricular restraint devices do not allow for either the measurement or adjustment of ventricular restraint level. Periodic adjustment of restraint level post-device implantation may improve therapeutic efficacy. We evaluated the feasibility of an adjustable quantitative ventricular restraint (QVR) technique utilizing a fluid-filled polyurethane epicardial balloon to measure and adjust restraint level post-implantation guided by physiologic parameters. QVR balloons were implanted in nine ovine with post-infarction dilated heart failure. Restraint level was defined by the maximum restraint pressure applied by the balloon to the epicardium at end-diastole. An access line connected the balloon lumen to a subcutaneous portacath to allow percutaneous access. Restraint level was adjusted while left ventricular (LV) end-diastolic volume (EDV) and cardiac output was assessed with simultaneous transthoracic echocardiography. All nine ovine successfully underwent QVR balloon implantation. Post-implantation, restraint level could be measured percutaneously in real-time and dynamically adjusted by instillation and withdrawal of fluid from the balloon lumen. Using simultaneous echocardiography, restraint level could be adjusted based on LV EDV and cardiac output. After QVR therapy for 21 days, LV EDV decreased from 133+/-15 ml to 113+/-17 ml (p<0.05). QVR permits real-time measurement and physiologic adjustment of ventricular restraint therapy after device implantation.

Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

Science.gov (United States)

Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

2014-10-01

This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.