Therapeutic action of an antioxidant in chronic emotional-pain stress in the rat

Chronic emotional pain stress in rats causes disturbances of the cardiovascular system function (increase in arterial pressure and in heart rate), typical of neuroses-like state, and changes of the vegetative nervous system reactivity tested with functional load by two-hour hypokinesis. Increase in spleen weight is observed as well as a tendency to adrenals weight increase, a decrease of Na, K-ATPase activity and activation of lipid peroxidation in cortical and hippocampal homogenates. Administration of F-801 antioxidant according to therapeutic scheme after the end of stress action, restores normal function of the cardiovascular system, normal reactivity of the vegetative nervous system, decreases adrenals weight and increases the weight of thymus and also normalizes ATPase activity and the level of lipid peroxidation. A backward correlation dependence of the Na, K-ATPase activity on the level of malondialdehyde in the brain tissue has been established.     

Effect of stress experienced during pregnancy on the rate of lipid peroxidation in erythrocytes and brain tissue of newborn rat pups

The rate of lipid peroxidation (LPO) in erythrocytes and brain homogenate has been assessed by the accumulation of malondialdehyde, the degree of erythrocyte autohemolysis, the content of hydrogen peroxide and catalase activity observed in newborn rats aged 1 hour, 1, 15, 20 and 30 days. Pregnant rats were exposed to emotional stress (aggressive interaction of two pregnant rats in an unavoidable conflict situation provoked by nociceptive irritation. Significant age-dependent differences in the rate of LPO (both in erythrocytes and cerebral tissue) have been found. The highest rate was noted in rats 15 days of age. The emotional stress of pregnant females resulted in the changes of behavioural reactions of newborn rats and LPO activity that was characterized by the increase in LPO rate in 1-hour- and 1-day-old rats and by slowing of LPO rate in 15-day-old rats. These phenomena were observed in erythrocytes and brain tissues of test animals.     

Disruptions in the blood system upon exposure to low-dose ionizing radiation depending on duration of emotional stress

In experiments on rats, disturbances in the development of blood system adaptive reactions on emotional stress were found. Under the combined effect of preliminary (before stress) exposure to 0.8 Gy of gamma-radiation and the emotional stress of various duration (2, 4 and 8 days), a compensatory capability of the blood system decreased. The degree of the disturbances directly depended on the duration of the emotional stress.     

Increased enzymatic activity of antioxidant protection of the heart in the adaptation of rats to short-term stress exposure

It has been shown that adaptation to short-term emotional-painful stresses leads to an increase in antioxidant enzyme activities but does not change vitamin E content in the myocardium. The most labile enzyme was catalase (35% increase). During stress in nonadapted animals the enzyme activity decreased, as compared to the control, while in the group of adapted animals with subsequent stress the activity was even higher than in the control. During initiation of lipid peroxidation in the heart homogenates in vitro there was a 3-fold increase and a 1%-fold decrease in the oxidation intensity in rats exposed to stress and in adapted animals, respectively. The role of adaptation activation of cardiac antioxidant system in the prevention of stress-induced heart damage is discussed.     

Apha-tocopherol in a complex with dimethyl sulfoxide--an agent possessing highly effective adaptogenic action in chronic emotional-pain stress in rats

Alpha-tocopherol (5 mg/kg) administered perorally with dimethyl sulfoxide (50 mg/kg) in chronic emotional pain stress in rats possesses an effective antistress action, exceeding the effects of these drugs administered separately. Their prophylactic complex administration prevents the hypertension produced by stress, disturbance of reactivity of the vegetative nervous system during functional load, change of the behaviour in the open field. Adaptogenic action of the drugs is accompanied by a reduction of the content of free-radical oxidation products and by raising of superoxide scavenging activity in the brain and blood serum, by raising of phospholipids content, lowering of cholesterol content and of the ratio of cholesterol phospholipids in the brain extracts.     

Comparative analysis of the stability of cardiovascular system functions in immobilized rats of different strains

The dynamics of arterial pressure and heart rate was studied in rats of different genetic lines (non-linear, Wistar, Way and August) during immobilization emotional stress. Different lines were characterised by different stability and ability of adaptation to emotional stress. Prognostic criteria were specified that enable to foresee at an early stage of emotional stress the disturbances of cardio-vascular control. The conclusion is made that resistancy against cardio-vascular disturbances during emotional stress is of genetic nature as well as may be due to characteristics of individual growth.     

Repeated Restraint Stress Induces Oxidative Damage in Rat Hippocampus

It has been shown that emotional stress may induce oxidative damage, and considerably change the balance between pro-oxidant and antioxidant factors in the brain. The aim of this study was to verify the effect of repeated restraint stress (RRS; 1 h/day during 40 days) on several parameters of oxidative stress in the hippocampus of adult Wistar rats. We evaluated the lipid peroxide levels (assessed by TBARS levels), the production of free radicals (evaluated by the DCF test), the total radical-trapping potential (TRAP) and the total antioxidant reactivity (TAR) levels, and antioxidant enzyme activities (SOD, GPx and CAT) in hippocampus of rats. The results showed that RRS induced an increase in TBARS levels and in GPx activity, while TAR was reduced. We concluded that RRS induces oxidative stress in the rat hippocampus, and that these alterations may contribute to the deleterious effects observed after prolonged stress.     

Consequences of the prenatal depletion of serotonin and stress on nociceptive sensitivity in rats

The long-term effects of serotonin (5-HT) synthesis alteration and of restraint stress experienced by pregnant Wistar rats on pain sensitivity (evaluated by the indices of the biphasic behavioral response in the formalin test) were studied in their 90-day-old offspring. Prenatal 5-HT depletion decreased pain sensitivity in one third of the rats and failed to change it in the rest of the rast. In these later, however, an obvious tendency for an increase of interphase duration in females and its decrease in males were revealed that indicates changing of the activity of the descending serotoninergic system modulating nociceptive signals at the level of the spinal dorsal horns. Prenatal stress decreased pain sensitivity in 50% of the rats with prenatal deficiency of 5-HT but increased it in the rest of the animals. Increase of pain sensitivity also occurred in the control rats but to a lesser extent (significantly in flexing + shaking behavior during the second phase) compared to the animals with prenatal 5-HT depletion. In the latter, sex differences were found in effects of prenatal stress on pain sensitivity. The present data point an important role of 5-HT in: 1) embryonic development of tonic nociceptive system which is modulated in the CNS by mechanisms differing from those of acute pain; 2) mediation of the prenatal stress influence on pain sensitivity in the formalin test in adult rats.     

8-weeks training program attenuates mitochondrial oxidative stress in the liver of emotionally stressed rats

In recent years it has been shown that emotional stress induced by immobilization may change the balance between pro-oxidant and antioxidant factors inducing oxidative damage. On the other hand, contradictory views exist concerning the role of physical activity on redox metabolism. Consequently, the present work was designed to assess the influence of an 8-week moderate swimming training program in emotionally stressed rats. Sixty 1-month-old male albino Wistar rats weighing 125-135 g were used in this experimental study. They were divided into three groups, as Control (lot A; n=20), Stressed (lot B; n=20) and Stressed & Exercised (lot C; n=20). Rats were stressed by placing the animals in a 25 x 7 cm plastic bottle 1 h/day, 5 days a week for 8 weeks. Protein carbonyl content values in liver homogenates were significantly increased in stressed animals (0.58+/-0.02 vs 0.86+/-0.03; p=0.018) which clearly indicated that emotional stress was associated with oxidative stress. Ultrastructural alterations, predominantly mitochondrial swelling and the decrease of cristae number observed by electron microscopy represented direct evidence of membrane injury. The most striking feature of our study was that we also found differences between stressed rats and stressed rats that performed our 8 week training program. Consequently our results highlight the potential benefit of a moderate training program to reduce oxidative damage induced by emotional stress since it attenuated protein oxidation and mitochondrial alterations.     

Model of emotional stress in rats

A new experimental rat model for suppression of release of arginine vasopressin (AVP) was evaluated. Release of AVP is potentiated by physiologic stimuli, but is suppressed by emotional stress. Rats were exposed to the aggressive behavior of other rats injected with 6-hydroxydopamine hydrochloride (6-OHDA) in both lateral ventricles and subjected to a pain stimulus applied to the tail. To ascertain whether emotional stress is induced by use of this method, plasma corticosterone, glucose, and AVP concentrations were measured in the stressed group of rats (n = 8) placed near a group of aggressive (fighting) rats. Characteristic changes in behavior, significant increases in plasma corticosterone and glucose values, and lack of increase in plasma AVP concentration in stressed rats confirmed that they experienced emotional stress. This new model meets the experimental requirements for suppression of AVP release in rats.     

Action of alcohol in chronic emotional pain stress in rats

Male albino rats were exposed to daily emotional painful stress (EPS) for 4 weeks. The arterial blood pressure of the stressed animals increased and the dynamics of the heart rate changed after functional loading (hypokinesis during one or two hours) as compared with the control group. The increase of the heart weight and activation of cytochrome oxidase activity in the cerebral cortex and hippocampus of rats exposed to EPS were also demonstrated. The use of 20% ethyl alcohol instead of drinking water during EPS partially prevented vegetative disturbances and activation of hippocampal cytochrome oxidase and fully prevented the heart hypertrophy and activation of the enzyme in the cortex. Alcoholization resulted in the increased weight of the spleen and brown adipose tissue and thymus involution. A possible mechanism of the antistress action of alcohol linked with normalization of intensified lipid peroxidation under stress is discussed.     

The effect of three hypolipidemic drugs on catalase activity and peroxisomal and mitochondrial palmitate oxidation in rat cardiac and skeletal muscle

Catalase activity and peroxisomal and mitochondrial palmitate oxidation have been investigated in cardiac and skeletal muscle from rats fed clofibrate, ciprofibrate or nafenopin in an unrefined diet for different periods of time. Nafenopin was also added to either a high carbohydrate (70% of kilocalories from glucose) or high fat (70% of kilocalories from lard) diet and fed to rats for either 1 or 3 weeks. Catalase activity was elevated in all muscles from rats fed the hypolipidemic drugs. The response of catalase activity in muscle to clofibrate was dose-dependent. The response time of catalase activity was different in individual muscles. Peroxisomal palmitate oxidation was elevated in the heart and soleus muscle from rats fed nafenopin in either the high-carbohydrate or the high-fat diet. There was no change in peroxisomal palmitate oxidation in psoas or extensor digitorum longus muscle from rats fed the drugs. Mitochondrial palmitate oxidation was only slightly increased by nafenopin in the heart and soleus muscles after 3 weeks of nafenopin feeding. The results suggest that the cardiac muscle, like the liver, responds to hypolipidemic drug treatment with an increase in peroxisomal fat oxidation. The skeletal muscle response is less specific and that tissue may not contribute to the hypolipidemic effect of the drugs. The findings also suggest that these drugs do not induce peroxisome proliferation in skeletal muscle.     

Evidence for lack of direct causality between pain and affective disturbances in a rat peripheral neuropathy model

Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague‐Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury [SNI]) and compared their performance in a battery of behavioral paradigms—anxiety, depression and fear memory—with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold [LT]), but 13% were similar to Sham controls (high threshold [HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI‐L) and right (SNI‐R) lesions and the lack of association between pain and behavior still remains. Left‐lesioned animals, independent of the LT or HT phenotype, presented increased anxiety‐like behaviors and decreased well‐being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes.     

Effect of mercury chloride on the level of lipids and products of their peroxidation in rat vital organs

The influence of mercury chloride on peroxidation processes of lipids and level of common lipids, phospholipids and spectrum of neutral lipids in liver, heart, lung and kidney of rats has been investigated. Administration of mercury chloride in a dose 0.7 mg/100 g of body weight to animals has invoked accumulation of lipids peroxide products in fractions of neutral lipids and phospholipids so it testifies the development of oxidative stress. Decrease of the most sensitive to oxidation fractions in the early stages of oxidative stress development and increase of free cholesterol and its ethers content in kidney and free cholesterol in the heart in more later terms as a result of mercury chloride administration have been revealed.     

Role of emotional stress in disorders of carbohydrate tolerance

Two series of rabbit experiments were carried out to study the influence of emotional stress on glucose tolerance. Relatively short-term (10 days) chronic emotional stress induced by prolonged (2 h daily) intermittent stimulation of negative emotiogenic zones of the hypothalamus through implanted electrodes led to decreased glucose tolerance. Repeated powerful emotional stresses induced by the clash of food and pain irritation did not pass traceless and manifested in the same glucose tolerance disturbances after a lengthy period of time (1 year).     

The effect of gonadectomy on interhemispheric asymmetry in rats

The influence was studied of the gonadectomy in the newborn and mature male and female rats on functional interhemispheric asymmetry of the reaction of avoidance of pain scream of another rat ("emotional resonance"), and motor and investigatory activity in the open field. Consecutive inactivation of the hemispheres was realized by K+ spreading depression. It has been shown that neonatally gonadectomized rats have no interhemispheric asymmetry of the studied reactions. In male rats gonadectomized in mature state, interhemispheric asymmetry of "the emotional resonance" reaction is not significant and in the motor and investigatory activity in the open field, in contrast to intact animals, the right hemisphere is dominant and not the left one. Ovariectomy of mature female rats led to the increase of the dominance of the left hemisphere in the control of "the emotional resonance" and change of the right hemispheric dominance in the control of the motor and investigatory activity in the open field for the left hemispheric one. Gonadectomy of male and female mature rats had an opposite effect on the functioning of the right hemisphere: facilitating in male rats and inhibitory in female ones.     

Peculiarities of Formation and Reversibility of Neurogenic Stress-Related Emotional Disorders in Rats

In experiments on rats, we modeled neurogenic stress-induced emotional disorders (stress was evoked by repetitive nociceptive stimulation) and studied their peculiarities within the stressory and post-stressory periods. In these animals, drastic changes in the brain electrical activity and emotional behavior gradually developed; such changes were manifested over a long time period after cessation of the stressory influences. Our experiments demonstrated that tight and stable interrelations among brain limbic structures and negative hypothalamic emotional centers are formed under conditions of prolonged action of emotional stress. This results in the development of a protracted state of negative emotional excitation. The hippocampus is considered one of the key limbic structures responsible for the development of stable pathological stress-related reactions of the brain. Within the post-stressory period, we observed dramatic worsening of the general functional state of the animals, which developed in a parallel manner with intensification of the activity of the negative emotiogenic brain system. It is probable that the existence of periods of unstable equilibrium between oppositely directed emotional reactions in the dynamics of stress and after cessation of stressory influences is a common rule. Such periods reflect peculiarities of rearrangements in the adaptive brain mechanisms under conditions of a stable change in the mode of brain functioning in one particular situation or another.     

Effect of chronic ethanol consumption on emotional stress in the white rat

Chronic pain emotional stress (PES), paired action of the white noise and electric skin stimulation and chronic (during 7 months) ethanol consumption in white rats were shown to act in the same direction. Hypertension, decrease of respiratory rate and increase of Hildebrandt index were observed as a result of PES, ethanol consumption, and especially under PES during ethanol consumption. Ethanol consumption by the animals led to their growth retardation and increase of the spleen and heart mass. Accidental thymus involution was noted both under ethanol consumption and PES. Activation of lipid peroxidation and decrease of superoxide dismutase activity (of its mitochondrial form especially) as well as of Na+,K+-ATP-ase activity were observed in brain homogenates of the rats after PES, while the general ATP-ase activity remained unchanged. An increase of triiodothyronine level and the tendency to thyroxine level increase as well as a decrease of superoxide dismutase activity were observed in the blood serum of these animals. A tendency towards lipid peroxidation level decrease and to brain superoxide dismutase activity increase, as well as blood antioxidation activity increase (evaluated by transferrin and coeruloplasmin contents and by serum superoxide dismutase activity) and a decrease of thyroxine level were observed as a result of ethanol consumption. The mechanisms are discussed of the "anti-stress" action of short-term ethanol consumption and of the action of its chronic consumption, additive to PES.