Neonatal stress in lambs: Behavioral and physiological responses

For the 1st 5 weeks after birth, experimental lambs reared in small flocks under conditions that approximated the normal social environment for sheep were subjected 3 times a week to an experimental procedure that was designed to expose the lambs to neonatal stress. The experimental procedure consisted of maternal separation, handling, and exposure to a Pavlovian conditioning paradigm. Each lamb responded to this experimental procedure with elevated plasma corticosteroid levels and intense vocalization. In contrast to the experimental (or neonatal stressed) lambs, the control lambs remained undisturbed with their mothers during the time the experimental lambs were being stressed. When both groups of lambs were subsequently exposed to open-field testing, the 2 groups did not differ in their behavioral responses (e.g., vocalization, latency to 1st movement, or locomotion) even though each of these behaviors has been found to be sensitive to the effects of neonatal social experience. Also no difference existed between the 2 groups in their initial adrenocortical response to open-field testing; however, the plasma concentration of corticosteroids of the experimental lambs took longer to return to pretest levels. At 5 months of age, the lambs were subjected to brief restraint in a dark chamber, and the effect of this brief stress on heart rate and plasma corticosteroids was measured. No differences were found between the 2 groups in either the heart rate or adrenocortical response to this stress. Thus, we have no evidence from these studies that neonatal stress had any effect on the lambs' subsequent ability to respond to brief behavioral stress.     

Behavioral and physiological consequences of intragastric oil feeding in rats

Four experiments were conducted to examine the appropriateness of intragastric feeding of vegetable oil. The first three experiments demonstrated that pairing intragastric feeding with a taste of saccharin, reduced subsequent saccharin preference slightly. A dose of lithium chloride which did not reduce food intake, produced a very strong conditioned aversion. It is therefore difficult to argue on the basis of taste aversions, that any reduction in food intake resulting from intragastric fat feeding is due to malaise. Intragastric fat feeding did not always reduce subsequent food intake; a large reduction in food intake was observed only when non-starved animals were given at least two previous spaced exposures to fat. The effects of oral and intragastric oil feeding on blood levels of triglycerides and free glycerol were examined. Blood triglycerides and glycerol rose sooner and fell sooner following intragastric than after oral oil feeding. Emulsifying the oil did not correct the abnormality; indeed it exaggerated the early rise in blood triglycerides and glycerol. These results indicate that interpretation of studies involving intragastric fat feeding is more complicated than generally recognized.     

Effect of chronic intracerebroventricular morphine to feeding responses in male rats

Stainless steel cannulae were implanted stereotaxically in the third ventricle of male albino rats. The rats were fed with natural food pellets and water ad lib. After seven days of cannulation, daily body weight, food intake and water intake were recorded for the first five days, which was considered the preinjection control. Then increased and repetitive injections of morphine sulphate were administered intracerebroventricularly (ICV) in dosage of 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter, 75 micrograms/5 microliter, 90 micrograms/6 microliter and 105 micrograms/7 microliter on each following day respectively. In a separate set of experiments, the blood glucose levels were measured in animals injected with morphine to a dose corresponding to 15 micrograms/1 microliter, 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter and 75 micrograms/5 microliter on days 1, 2, 3, 4 and 5 respectively. Statistically significant (p less than 0.001) decreases in the body weight, food intake, water intake and increase in blood glucose were observed. The inferences derived from the above observations for the possible involvement and interaction of opioids in the regulation of feeding mechanisms have been discussed.     

Behavioral and physiological responses of dairy goats to isolation.

Eight Nubian and eight Alpine dairy goat does were used in a crossover experimental design to determine the effect of 30 min of isolation on behavior and plasma concentrations of thyroxine (T4), triiodothyronine (T3), cortisol, norepinephrine (NOR), and epinephrine (EPI). Isolation was hypothesized to produce an emotional state analogous to fear. Focal animal behavior was recorded for the initial five min of isolation. Blood samples were obtained via jugular cannulae at 0 (immediately prior), 10, 20, 30 (during isolation), 40, 50 and 60 min (after return to their group). Response to isolation was characterized physiologically by increased plasma concentrations of NOR (p less than 0.01), but not T3, T4, cortisol or EPI, indicating a sympathetic discharge. Isolated goats also vocalized more frequently (p less than 0.01) and spent a greater amount of time sniffing, trotting and rearing (p less than 0.05). The Nubian does reacted more strongly (elevated NOR, trotting and rearing, p less than 0.01) to isolation than the Apline does.     

Behavioral and physiological effects of chronic mild stress in female rats

Anhedonia, a core symptom of clinical depression, refers to the loss of interest in normally rewarding stimuli; the chronic mild stress paradigm, an animal model of depression, was designed with this as an underlying feature. The procedure consists of the administration of a variety of ecologically relevant stressors over long durations. Its effects have been thoroughly investigated in male but not female rats. This study examines the appropriateness of stressors designed to evaluate the development and progression of depression in two strains of female rats, the effectiveness of two measures of anhedonia, and the relationship between stress reactivity and the estrous cycle. Changes in hedonic status were indexed for three weeks following a three week baseline period using two standard behavioral measures of anhedonia: sucrose intake and preference and thresholds for brain stimulation reward. Decreases in 24 h sucrose intake were observed in both strains during the first week of stress manipulations, and continued to decline thereafter for the remainder of the stress phase; in contrast, sucrose preference was unaffected by the stressors, indicating an overall reduction in fluid intake. No changes in the thresholds for brain stimulation reward were observed. The cyclical pattern of estrous was altered in both strains with a significant reduction in the number of regular cycles as a consequence of both the stressors and brain stimulation reward. Furthermore, cyclicity was not reinstated in many animals even six weeks after stress manipulations and behavioral tests had ceased. While the physiological measures suggest that the mild stressors are disruptive to female rats, the results of the behavioral tests are not consistent with the notion that the stressors induce an anhedonic state.     

Behavioral and physiological responses of dairy goats to food thwarting.

Eight Nubian dairy goat does in one experiment, and eight Alpine dairy goat does in a second experiment, were randomly allotted to food-thwarted or fed groups in a crossover experimental design. Food thwarting was hypothesized to produce an emotional state analogous to frustration. After a 1-week training period during which the goats of both breeds were conditioned to being simultaneously fed in adjacent feeding stalls, frustration was induced in half the goats by feeding only alternate does. Focal animal behavior was recorded for the initial five min after feeding frustration commenced. Blood samples were collected via a jugular cannula before, during and after frustration was induced for thyroxine (T4), triiodothyronine (T3), cortisol, norepinephrine (NOR), and epinephrine (EPI) determinations. Food thwarting was characterized by increased plasma concentrations of NOR, and increased incidences of pawing, head movements, mouthing of objects, behaviors directed toward neighboring does being fed, and rearing (p less than 0.01). When data were pooled across experiments, breed had a strong influence on cortisol (p less than 0.05), with Nubian does having higher concentrations regardless of treatment. Concentrations of hormones were not significantly correlated with behaviors. These findings suggest that frustration may elicit a discharge of NOR but not EPI.     

Differential hormonal and physiological responses to stress in Roman high- and low-avoidance rats

In the present experiments, plasma concentrations of corticosterone, ACTH, prolactin, blood glucose, serum free fatty acids, core temperature and fecal boli were measured immediately following the exposure of Roman high- and low-avoidance rats (RHA/Verh, RLA/Verh) to various stressful situations. As compared to RLA/Verh rats, the RHA/Verh animals showed an attenuated emotional response in “non-self-menacing” (novel environment) situations. Differences between the 2 selected lines were not generally found in unstressed rats or in “high-stress” (ether, immobilisation, footshock) situations.     

Subjective and physiological responses to emotion-eliciting pictures in male schizophrenic patients.

Several studies have shown that schizophrenic patients have difficulties in their ability to recognize emotional facial expressions, whereas other research indicated that they subjectively report the same emotional experience as healthy controls. The purpose of this study was to investigate whether the physiological responses that accompany emotions differ between schizophrenic patients and controls, which would suggest a different basic emotional processing mechanism in these patients. We presented 40 emotion-eliciting pictures to male patients (n=26) and controls (n=21), while measuring heart rate (HR), breathing rate (BR), skin conductance response (SCR) and systolic blood pressure (SBP). Each subject rated each picture for its degree of valence and arousal. Mixed-effects regression models were used to investigate the relationships between the subjective ratings and the physiological responses. In both groups, BR and SCR increased with increasing arousal ratings, suggesting sympathetic activation. The SBP of both groups increased with increases in both the valence and the arousal ratings. However, whereas the patients' HR first decreased with decreasing pleasure ratings and subsequently increased with higher arousal and valence ratings, the HR in the control group was influenced by a complex interaction between valence and arousal ratings. Thus, the schizophrenic patients showed similar relationships between subjective ratings and SCR, BR, and SBP, but a different relationship between subjective ratings and HR compared with the healthy controls.     

Behavioral responses to partial-gravity conditions in rats

The effects of microgravity or hypergravity on living organisms have been studied extensively; however, thus far no studies have addressed the effects of “partial-gravity”, that is, the low-gravity levels between the unit gravity (1 G) on Earth and zero gravity (0 G) in space. The purpose of the present study was to examine behavioral responses in rats under partial-gravity conditions. Rat behavior was monitored by video cameras during parabolic flights. The flight trajectory was customized in order to generate graded levels of partial gravity. Gravity-dependent behavior patterns were observed in rats. In the conditions of 0.4 G through 0.2 G, rats showed startle and crouching. Hindlimb stretching emerged at 0.15 G and was more frequently observed toward 0.01 G. Different thresholds may exist for emotional and balance/posture-related behaviors.     

Behavioral and physiological responses to dipsogens: A comparative analysis

Rats, gerbils and guinea pigs had water intake and vascular conditions measured after various dipsogenic challenges. Species drank equal (per body weight) volumes of water to extracellular stimuli, but drank differentially to water deprivation and cellular challenges. Rats' drinking following water deprivation was associated with hyperosmolality, while gerbils' and guinea pigs' drinking was closely associated with weight loss. Rats and gerbils represented extremes in response to cellular stimuli, rats showed the lowest drinking thresholds (increased osmolality) — greatest drinking, gerbils showed the highest thresholds — least drinking. Manipulation of renal function resulted in near equivalence of response to cellular stimuli for rats and gerbils. The results are discussed in terms of species similarity and dissimilarity of response to dipsogenic challenges.     

Behavioral and cardiac responses to mild stress in young and aged rats: effects of amphetamine and vasopressin.

Young (3-month-old) male Wistar rats showed a relative decrease in heart rate to a sudden silence superimposed on low intensity background noise. This bradycardia was accompanied by immobility behavior. In 26-month-old rats the magnitude of the heart rate response was reduced while immobility behavior remained in the same order of magnitude as in young controls. In the aged rats a shift in autonomic regulation of heart rate in the direction of increased sympathetic influence was indicated by the results obtained by blocking the autonomic input with atropine methyl-nitrate (0.5 mg/kg) or atenolol (1 mg/kg) given subcutaneously (SC) 30 min prior to testing. Pretest (30 min) administration of amphetamine (0.5 mg/kg SC) reinstated the bradycardiac response in aged rats to a level seen in young ones. Arginine-vasopressin (AVP, 10 micrograms/kg SC), administered 60 min before the experiment, markedly facilitated the cardiac response in young animals but failed to restore cardiac responses in aged ones. The immobility behavior in the peptide-treated aged rats was also absent. The present findings suggest that a diminished central aminergic drive in aged rats is causing a reduction of the parasympathetic cardiac response to stress of sudden silence. The results also indicate an age-related vasopressinergic modulation of behavioral and cardiac responses to mild stress.     

Central serotonin depletion modulates the behavioural, endocrine and physiological responses to repeated social stress and subsequent c-fos expression in the brains of male rats.

Intraspecific confrontation has been used to study effect of depleting central serotonin on the adaptation of male rats to repeated social stress (social defeat). Four groups of adult male rats were used (serotonin depletion/sham: stressed; serotonin depletion/sham: non-stressed). Central serotonin was reduced (by 59-97%) by a single infusion of the neurotoxin 5,7-dihydroxtryptamine (150 microg) into the cerebral ventricles; levels of dopamine and noradrenaline were unaltered (rats received appropriate uptake blockers prior to neurotoxic infusions). Sham-operated animals received solute only. Rats were then either exposed daily for 10 days to a second larger aggressive male in the latter's home cage, or simply transferred to an empty cage (control procedure). Rats with reduced serotonin failed to show the increased freezing behaviour during the pre-defeat phase of the social interaction test characteristic of sham animals. There was no change in the residents' behaviour. Core temperature increased during aggressive interaction in sham rats, and this did not adapt with repeated stress. By contrast, stress-induced hyperthermia was accentuated in serotonin-reduced rats as the number of defeat sessions increased. Basal core temperature was unaffected by serotonin depletion. Heart rate increased during social defeat, but this did not adapt with repeated stress; serotonin depletion had no effect on this cardiovascular response. Basal corticosterone was increased in serotonin-depleted rats, but the progressive reduction in stress response over days was not altered. C-fos expression in the brain was not altered in control (non-stressed) rats by serotonin reduction in the areas examined, but there was increased expression after repeated social stress in the medial amygdala of 5-HT depleted rats. These experiments show that reduction of serotonin alters responses to repeated social stress in male rats, and suggests a role for serotonin in the adaptive process.     

Cardiovascular responses to acute footshock stress in adult and aged Fischer 344 male rats

Tail artery catheters were surgically implanted in Fischer 344 male rats to allow for measurement of mean arterial pressure (MAP, mm Hg) and heart rate (HR, beats/min) in conscious, unrestrained rats. Basal values of MAP and HR were similar for groups of 4, 12 and 24 month old rats. Increments in Map did not differ among rats of the 3 ages following handling and transfer to a shock chamber or immediately or 5 minutes after exposure to inescapable footshock (2.0 mA, 0.6 sec duration, every 6 sec for 1 min). In contrast, there was a significant age-related attenuation of the tachycardia following handling and transfer of rats to the shock chamber and at the end of footshock. These data are consistent with previous findings of a reduced sensitivity of the aged myocardium to stress-induced sympathetic stimulation.     

Behavioral and physiological responses of female house mice to foraging variation

Peripubertal female house mice were required to work for their food at either 23 degrees C or 9 degrees C. We used a special caging system in which animals had to emerge from a thermally-buffered burrow and run a programmable number of running wheel revolutions to obtain a pellet of food. Of concern here were the behavioral and physiological adjustments necessary to accommodate growth and reproductive development when faced with the need to forage for different lengths of time at different temperatures. When female house mice are confronted with poor foraging at cool temperatures they allot their highest priorities to maintaining energy balance; body growth is next, and reproductive development and nonforaging activity have the lowest priorities. Our results also demonstrate that the time spent foraging while exposed to low ambient temperature is critical for this species. This relationship probably determines whether or not house mice will breed continuously or seasonally in a particular habitat.     

Altered responses to environmental stress in streptozotocin-diabetic rats.

Metabolic and biochemical adaptations were compared in streptozotocin-diabetic and nondiabetic control rats exposed for 24 hours to a cold environment (4 degrees C) or hypobaric hypoxia (simulated altitude = 12,000 ft). In the cold, diabetic rats had greater reductions in adrenal norepinephrine (NE) and greater elevations in urinary NE and epinephrine excretion. However, diabetics did not increase food intake, whereas cold-exposed nondiabetic rats did. 5-HT turnover was reduced in hypothalamus and elevated in brain stem in both diabetics and nondiabetics. Responses to hypoxia were different. Both diabetics and nondiabetics reduced food and water intake and had elevated plasma glucose concentrations. Diabetics had elevated urinary NE excretion. Hypothalamic NE concentration and dopamine turnover were significantly reduced by hypoxia. Brain stem 5-HT turnover was also reduced in nondiabetics but not in diabetics. Thus, diabetics had a different response profile to the environmental stressors than nondiabetics. In addition, the two stressors elicited different responses. Some stressors may be more debilitating in diabetics. The greater reactivity of the sympathetic nervous system in diabetics suggests a mechanism by which stress leads to increased risk of metabolic complications in diabetes mellitus.     

Pharmacokinetics and feeding responses to muramyl dipeptide in rats

N-acetyl-muramyl-L-alanine-D-isoglutamine or muramyl dipeptide (MDP) is the minimally active subunit of bacterial peptidoglycan. During a systemic infection, the involvement of MDP has been demonstrated in food intake depression by the macrophage hydrolysis of Gram-positive bacteria. Under normal conditions, mammals are constantly exposed to the release of endogenous MDP from degraded gut flora and that of exogenous MDP from the diet. However, MDP digestion and absorption in the gastrointestinal tract are not fully understood, and their physiological significance needs to be clarified. After gavage (1.5 mg/kg), very low levels of MDP were found in the systemic circulation of rats and feeding patterns were not altered. In contrast, after the intraperitoneal injection of a similar dose, a depression in food intake was observed. The rats reduced their meal frequency and constant feeding rate, showing signs of satiety. The behavioral satiety sequence (BSS) was modified by behavioral changes, similar to those which appear during sickness, such as an increase in resting and a reduction in grooming. Our data suggest that the hypophagic effect of MDP may result from satiety and sickness behavior.     

Prenatal immobilization stress and postnatal maternal separation cause differential neuroendocrine responses to fasting stress in adult male rats

Prenatal immobilization stress (PNS) and postnatal maternal separation (MS180) are two widely used rodent models of early-life stress (ELS) that affect the hypothalamus–pituitary–adrenal (HPA) axis, cause behavioral alterations, and affect glucose tolerance in adults. We compared anxiety-like behavior, coping strategies, and HPA axis activity in PNS and MS180 adult (4-month-old) male rats and assessed their glucose tolerance and HPA axis response after mild fasting stress. Both PNS and MS180 induced a passive coping strategy in the forced swimming test, without affecting anxiety-like behavior in the elevated plus-maze. Moreover, both PNS and MS180 increased the hypothalamic corticotropin-releasing hormone expression; however, only MS180 increased the circulating corticosterone levels. Both early life stressors increased fasting glucose levels and this effect was significantly higher in PNS rats. MS180 rats showed impaired glucose tolerance 120 min after intravenous glucose administration, whereas PNS rats displayed an efficient homeostatic response. Moreover, MS180 rats showed higher circulating corticosteroid levels in response to fasting stress (overnight fasting, 12 hr), which were restored after glucose administration. In conclusion, early exposure to postnatal MS180, unlike PNS, increases the HPA axis response to moderate fasting stress, indicating a differential perception of fasting as a stressor in these two ELS models.     

Chronic stress in dogs subjected to social and spatial restriction. I. Behavioral responses.

Six weeks of social and spatial restriction were used as a model to induce chronic stress in Beagles. Behavioral and physiological measurements were performed during a period of enriched spacious outdoor housing in groups (GH) and during a subsequent period of solitary housing in small indoor kennels (IH). Behavioral parameters that may indicate chronic stress in dogs are reported. During IH, the dogs showed significantly (comparison-wise error rate <0.05) lower postures than during GH. IH induced enduring increments in frequencies of autogrooming, paw lifting, and vocalizing, and was associated with incidents of coprophagy and repetitive behavior. So far, we interpret the behavioral changes as signs of chronic stress. Relatively low levels of walking, digging, intentions to change from one state of locomotion to another, and increments in circling are conceived as obvious adaptations to the specific features of the IH system. By challenging the dogs outside their home kennel we tested whether the dogs' coping abilities were affected by IH. Dogs that were challenged were introduced into a novel environment, given the opportunity to escape from their home kennel, restrained, walked down an unfamiliar corridor, presented a novel object, exposed to loud noise, given food, or confronted with a conspecific. During IH, challenged dogs exhibited higher postures, showed more tail wagging, nosing, circling, urinating, and defecating, and changed more often from one state of locomotion (or posture) to another than during GH. These behavioral changes were observed across the different types of challenges, with the exception of the noise administration test. In the presence of conspecifics, the socially and spatially restricted male dogs behaved more dominantly and aggressive than during the time that they were kept in groups. Such behavior manifested as increased performances of raised hairs, growling, paw laying, and standing over. Both sexes showed increases in paw lifting, body shaking, ambivalent postures, intentions to change from one state of locomotion to another, and trembling in any of the challenges, excluding the walking down the corridor test. In short, during a variety of challenges, socially and spatially restricted dogs exhibited a heightened state of aggression, excitement, and uncertainty. Behavioral differences between dogs that had experienced pleasant and bad weather conditions during GH, suggested that "pleasant-weather individuals" had experienced early stress during the control period, and, as a result, responded to the subsequent period of IH differently. Regardless of the housing conditions, challenged bitches showed stronger indications of acute stress than male dogs. Gender did not affect the chronic stress responses to social and spatial restriction. A low posture and increased auto-grooming, paw lifting, vocalizing, repetitive behavior, and coprophagy may indicate chronic stress in dogs, and as such, can help to identify poor welfare. When challenged, chronically stressed dogs may show increased excitement, aggression, and uncertainty, but the nonspecificity of such emotional behavior will complicate its practical use with regard to the assessment of stress.     

Neurochemical, endocrine and immunological responses to stress in young and old Fischer 344 male rats

Two experiments were performed. In the first, a 20 min conditioned emotional response (CER) paradigm was used to compare the neurochemical, endocrine and immunological responses to stress of 7- and 22-month-old Fischer 344 (F344) male rats. In the second, corticosterone levels 20 min following ether stress, and regional brain type I and II corticosterone receptor densities were examined using 7- and 17.5-month-old F344 male rats. Dopamine (DA) metabolism in old nonstressed rats was significantly reduced in the medial frontal cortex, neostriatum, nucleus accumbens and hypothalamus, but not in the amygdala. The CER procedure, nevertheless, increased medial frontal cortical, nucleus accumbens and amygdaloid DA turnover in both the young and old rats. The young and old nonstressed rats did not evidence differences in norepinephrine (NE) and serotonin (5-HT) concentrations. However, stress resulted in a decrease in medial frontal cortical 5-hydroxyindoleacetic acid (5-HIAA) and hypothalamic 5-HT levels in old but not in young animals. These observations suggest age-related differences in the response of central NE and 5-HT systems to stress. Ether and the CER procedure led to exaggerated corticosterone responses in the old rats (17.5 and 22 month, respectively). Hippocampal type I but not type II corticosterone receptors were decreased by 47% in the 17.5-month-old rats. Thus, age-related changes in hippocampal corticosterone receptor types do not occur in unison, and the exacerbated corticosterone response to stress precedes the reported down-regulation of hippocampal type II corticosterone receptors in aged rats. Age-related changes were not observed in the concentrations of corticosterone receptors in other brain regions, or in the prolactin response to stress. The old rats, however, evidenced a reduction in the availability of the renin substrate, angiotensinogen, and in stress-induced renin secretion. Immune function was impaired in the old nonstressed rats, and further compromised by exposure to the CER procedure. In comparison to the young control rats, the old nonstressed rats showed an increased percentage of splenic large granular lymphocytes, reduced splenic natural killer cytotoxicity, and impaired Con-A-stimulated splenic T lymphocyte proliferation. Reductions in T splenic cell proliferation and natural killer cytotoxicity were observed in the young rats subjected to the CER paradigm, but not to the same extent as in the old rats. These observations indicate that aging male F344 rats evidence major alterations in basal central monoamine, endocrine and immune functions, and an increased sensitivity of these systems to stress.     

高脂饮食诱发血糖升高的动物模型中瘦素与胰岛素变化的关系

高脂饲料喂养大鼠,诱发胰岛素抵抗形成血糖升高,以研究瘦素与糖尿病的关系。将大鼠分为正常和高脂饲料喂养组,于喂养前及喂养30、60d时测血糖、瘦素与胰岛素水平,行高胰岛素正常血糖钳夹试验,最后分离分离脂肪称重。结果：高脂饮食组具有明显的胰岛素抵抗,有50％血糖升至8．3mmol/L以上;形成糖尿病的大鼠体重与对照组无明显区别;高脂饮食组瘦素与胰岛素水平与对照组比较有明显差异;所有大鼠瘦素水平与体重、胰岛素、血糖均呈正相关。结论：（1）高脂饮食是导致胰岛素抵抗形成糖尿病的诱因之一;（2）体脂含量与糖尿病正相关;（3）瘦素抵抗与胰岛素抵抗形成糖尿病的发病机制可能有关;（4）瘦素水平随着鼠龄的增加而增高,且参与体重的调节。