Expression of the c-fos Gene during Emotional Stress in Rats: The Clocking Effect of Delta Sleep-Inducing Peptide

Emotional stress induced more marked increases in the expression of the c-fos gene in limbo-reticular structures of the brain in rats prognostically predisposed to emotional stress. I.p. doses of delta sleep-inducing peptide (DSIP) (60 nmol/kg) weakened the stress-induced expression of the c-fos gene. This effect was more apparent in animals predisposed to emotional stress, in which preliminary injections decreased stress-induced c-fos expression in the paraventricular hypothalamus and the medial and lateral parts of the septum. The decreased expression of the early gene c-fos in emotional stress after preliminary dosage with DSIP may reflect the leading mechanism of the anti-stress action of this peptide.     

Structural-Functional Organization of Neurons in the Cerebral Cortex of Rats with Different Levels of Resistance to Emotional Stress in Conditions of Exposure to Delta Sleep-Inducing Peptide

Wistar rats with different levels of resistance to emotional stress (ES) were subjected to stress and brain sections stained with Nissl cresyl violet were used for quantitative analysis of the structural organization of neurons in layer V of the sensorimotor cortex. Some animals received delta sleep-inducing peptide (DSIP) 1 h before stress. Control ES-susceptible rats, as compared with resistant rats, had lower levels of normochromic and moderately hypochromic neurons. Normochromic neurons were not seen after stress. Rats susceptible to ES showed particularly sharp decreases in moderately hypo- and hyperchromic neurons, along with increases in the proportions of extremely hypo- and hyperchromic neurons, ghost cells, and ischemically altered cells. After administration of DSIP before stress, ischemically altered cells were not seen in any group: the level of reduction of extremely hyperchromic neurons was smaller in ES-susceptible rats than in ES-resistant rats. It is suggested that brain hypoxia plays a particular role in disorganizing the cortex in conditions of ES, while DSIP has both antistress and antihypoxic properties.     

Changes in Duodenal Lymphoid Structures in Rats with Different Levels of Behavioral Activity Treated with Delta Sleep-Inducing Peptide and during Acute Emotional Stress

The effects of delta sleep-inducing peptide (DSIP) on intestinal lymphoid formations were studied. Experiments were performed on 42 male Wistar rats which had previously been tested in an open field. The results of this test were used to divide the rats into behaviorally active (predicted to be stress-resistant) and passive (stress-susceptible) animals. Stress was applied by restraining the animals in boxes with electrical stimulation of the back for 1 h. Administration of i.p. DSIP to rats led to decreases in the number of eosinophils in animals of all experimental groups. In active rats of the control group, administration of DSIP produced increases in the numbers of small and intermediate lymphocytes which were greater than increases in passive rats. After acute stress, behaviorally active rats showed increases in the number of lymphoid cells, mainly due to small and intermediate lymphocytes. In passive rats, stress and injection of DSIP were followed by increases in the numbers of plasma cells in all the duodenal mucosal structures studied.     

Effect of delta-sleep inducing peptide on electrical instability of the heart in emotional stress

The effect of the delta-sleep inducing peptide (DSIP) on disorders of the cardiac rhythm in emotional stress was studied in experiments on rabbits. DSIP (60 nmol/kg) diminished or arrested ventricular extrasystole occurring in experimental emotional stress. It was shown that the antiarrhythmic effect of DSIP is most manifest if it is injected just before exposure to the stress factors. DSIP injection induces increase of the thresholds of the occurrence of ventricular fibrillation and its precursors in intact animals. This can explain the high preventive effect of DSIP in stress. The acquired data on the antiarrhythmic effect of DSIP should be taken into consideration in elaborating preventive recommendations aimed at raising the organism's stability to stress factors.     

Modulating Effect of Interleukin-4 on Free Radical Processes in the Brain of Rats during Emotional Stress

We studied the effect of anti-inflammatory cytokine IL-4 on the intensity of free radical processes in emotiogenic brain structures (hypothalamus, sensorimotor cortex, and amygdala) in rats with different prognostic emotional resistance. One-hour immobilization of animals with simultaneous electrocutaneous stimulation was used as a model of acute stress. The stress was accompanied by accumulation of MDA (LPO end-product) in the sensorimotor cortex and amygdala of passive rats. Intraperitoneal administration of IL-4 (5 μg/kg) increased MDA content in the amygdala and hypothalamus of non-stressed rats with different behavioral activity. In the sensorimotor cortex of passive and, especially, active rats, a decrease in MDA level was observed after injection of this cytokine. Preliminary administration of IL-4 prevented LPO activation in the sensorimotor cortex of behaviorally passive animals observed after stress against the background of saline injection. Regional peculiarities of LPO under the influence of this cytokine can be determined by differences in both biochemical processes in the brain tissue and specific involvement of different emotiogenic structures in the formation of the stress response. The revealed differences in the effects of IL-4 on free radical processes in active and passive rats indicate peculiarities of immune mechanisms in animals with different resistance to the same type of stress.     

Functional role of the neurospecific S-100 protein in the processes of memory

The change in the content of S-100 protein in the brain in the presence of learning and an amnestic influence (administration of an M-cholinolytic), taking interhemispheric asymmetry into account, was studied in experiments on white rats. The action of S-100 protein and of an antiserum to this protein on the learned behavior of the rats were also investigated. It was established that the level of S-100 protein increases in the left and right hemispheres in the process of the development of an alimentary conditioned reflex. The disruption induced by the cholinolytic of the processes of the development of conditioned reflexes is accompanied by a decrease in the content of S-100 protein in the brain. Intracisternal administration of an M-cholinolytic and an antiserum to S-100 protein mutually potentiates their amnestic effect.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 41, No. 1, pp. 60–65, January–February, 1991.     

Structural and functional organization of the cerebral cortex neurons in rats with various resistance to emotional stress following administration of delta-sleep-inducing peptide

In Wistar rats with different resistance to emotional stress (ES), subjected to stress exposure (SE), the structural organization of neurons in layer V of sensomotor cortex was studied quantitatively in brain sections stained using Nissl's cresyl violet method. One group of animals was injected with delta sleep-inducing peptide (DSIP) 1 hr before SE. In rats of control group predisposed to ES, the amount of normochromatic and moderately hypochromatic neurons was decreased as compared to the rats resistant to ES. After SE, normochromatic neurons were not demonstrated. In rats predisposed to ES, the contents of moderately hypo- and hyperchromatic neurons was found to fall dramatically with a simultaneous increase in the number of extremely hypo- and hyperchromatic neurons, ghost cells and ischemically changed cells. After DSIP infusion before SE, ischemically damaged cells were not found in any group, while the degree of shrinkage of extremely hyperchromatic neurons was lower in rats predisposed to ES as compared to rats resistant to ES. It is suggested that brain hypoxia plays an important role in cortex disorganization during ES, whereas DSIP, possesses both antistress and antihypoxic effects.     

Lipid peroxidation and antioxidant enzymes in the brain of rats exposed to acute emotional stress: Effect of interleukin-1β

Acute emotional stress is shown to raise the level of malonic dialdehyde in the hypothalamus of August rats. After intraventricular administration of interleukin-1β, the malonic dialdehyde level and the activity of antioxidant enzymes tended to rise selectively in the hypothalamus (but not in the sensorimotor cortex) of August, Wistar, and WAG rats. In the presence of this interleukin, acute emotional stress did not cause increases in lipid peroxidation products in the hypothalamus of August rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 244–247, September, 1995     

Intensity of Oxidative and Antioxidant Processes in the Brain of Rats with Various Behavioral Characteristics during Acute Stress

We studied the effect of acute emotional stress (1-h immobilization with simultaneous electrocutaneous stimulation) on the prooxidant-antioxidant balance in emotiogenic structures of the brain in rats with various behavioral characteristics. TBA-reactive substance content in the hypothalamus of rats remained practically unchanged after stress exposure. Opposite change in activity of antioxidant defense enzymes in this structure of the brain in behaviorally active specimens probably compensate for the possible variations in LPO during emotional stress. Activities of glutathione reductase and Cu/Zn-containing SOD in the hypothalamus of passive animals decreased under these conditions. As differentiated from active rats, emotional stress in passive specimens was accompanied by the accumulation of TBA-reactive substances in the sensorimotor cortex and amygdala. The observed increase in glutathione peroxidase activity in passive animals probably serves as a secondary compensatory reaction to LPO activation. Our results illustrate specific changes in free radical processes and antioxidant defense in emotiogenic structures of the brain in rats with various behavioral characteristics after acute stress. These changes were more pronounced in behaviorally passive specimens than in active animals. It was probably related to differences in the oxidative status of CNS in rats with various prognostic resistance to similar stress factors.     

Effect of Interleukin-1β on Lipid Peroxidation in Emotiogenic Structures of the Brain in Rats during Acute Stress

We studied the effects of immunomodulatory cytokine interleukin-1β on lipid peroxidation in emotiogenic structures of the brain (hypothalamus, sensorimotor cortex, and amygdala) of behaviorally active and passive rats with different prognostic resistance to stress. Immobilization of animals with simultaneous electrocutaneous stimulation (1 h) served as the model of acute emotional stress. Intraperitoneal injection of IL-1β (5 μg/kg) was followed by accumulation of malonic dialdehyde (end-product of lipid peroxidation) in all structures of the brain in passive rats, as well as in the hypothalamus of active animals. As differentiated from active rats, stress exposure in passive specimens was accompanied by a selective increase in malonic dialdehyde content in the sensorimotor cortex and amygdala. Pretreatment with IL-1β prevented activation of lipid peroxidation in the studied structures of the brain in passive rats after stress exposure. Our results show the specifi c effect of IL-1β on free-radical processes in the hypothalamus, sensorimotor cortex, and amygdala in rats with various behavioral parameters. Regional features of lipid peroxidation in emotiogenic structures of the brain in animals with different emotional reactivity probably contribute to the existence of signifi cant variations in the individual resistance to emotional stress.     

Resistance to Neurodegenerative Brain Damage in August and Wistar Rats

In Wistar and August rats characterized by different resistance to acute emotional stress we compared the resistance to neurodegenerative brain damage (model of Alzheimer’s disease) produced by administration of a neurotoxic peptide fragment (25–35) β-amyloid into the brain. August rats were more resistant to acute stress and development of neurodegenerative disorders compared to Wistar rats. This conclusion was derived from studying animal behavior in conditioned passive avoidance task and open-field test that characterize cognitive function of the brain. Administration of β-amyloid modulated the behavior of Wistar rats, which reflected the impairment of memory and orientation and exploratory activity in these animals. These disturbances in Wistar rats were accompanied by activation of lipid peroxidation in the hippocampus.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 5, pp. 491–494, May, 2005     

Mechanisms of the Influences of the Central Administration of Substance P on Ethanol Consumption in Chronically Alcoholic Rats

The effects of central administration of substance P (SP) on alcohol consumption and dopamine metabolism in the projections of the mesocorticolimbic and nigrostriatal systems of the brain were studied in chronically alcoholic rats. Rats received 15% ethanol solution for 6 months without choice. Intraventricular administration of SP (1 g/rat) decreased consumption of 10% ethanol solution by 41% compared with controls in an alcohol free choice test lasting one day. After chronic alcoholism, there was a decrease in the ratio of dihydroxyphenylacetic acid (DOPA) and homovanillic acid (HVA) to dopamine in the nucleus accumbens and striatum in rats subjected to alcoholism, as compared with intact controls. Chronically alcoholic rats treated with SP showed increases in DOPA, HVA, and the DOPA:dopamine and HVA:dopamine ratios in the nucleus accumbens as compared with animals given physiological saline, by 17%, 23%, 9% and 19% respectively. The only increases in the striatum were in the absolute levels of DOPA and HVA, by 28% and 29%, while the ratios of these metabolites to dopamine remained unchanged. Thus, central administration of SP decreased the voluntary consumption of ethanol in the ethanol free choice test and enhanced dopamine metabolism in structures of the mesolimbic and nigrostriatal systems in chronically alcoholic rats.     

Changes in the protein content in hypothalamic neurons of neonatally castrated sexually mature male rats

Changes in the protein content in neurons of the anterior and mediobasal hypothalamus of neonatally castrated sexually mature rats were demonstrated by an interferometric method. A considerable increase in the dry weight of the neurons was found in the medial preoptic region and the arcuate and ventromedial nuclei of the hypothalamus. The clearest changes were observed in the nuclei of these neurons. The results point to an influence of androgens in the period of sexual differentiation of the brain on hypothalamic structures responsible for the regulation of both the cyclic and the tonic secretion of gonadotropic hormones in sexually mature animals.Laboratory of Hormoral Rugulation, Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 586–589, November, 1978.     

Pentagastrin modulation of sensitivity of neurons of the lateral hypothalamus to noradrenaline and dopamine

The chemical sensitivity of neurons of the lateral hypothalamus of hungry and fed rabbits to pentagastrin (PG) and to the mediators, noradrenaline (NA) and dopamine (DA), was investigated utilizing indices which permit the assessment of the structural-functional organization of the impulse stream of nerve cells. It was demonstrated that the neurons of the lateral hypothalamus possess varied chemical sensitivity in the presence of alimentary motivation and during the satisfaction of the corresponding need. The microiontophoresis of PG changes the sensitivity of cells in hungry animals to a higher degree to DA (60%) than to NA (30%), while in fed animals, to a higher degree to NA (48%) than to DA (23%). The administration of NA against the background of the action of PG to fed rabbits decreased the percent of neurons with spike train complex activity. The number of cells in the deprived animals with impulse activity of a similar character decreased following the microiontophoresis of DA alone and DA against the background of the action of PG. It is concluded that PG exerts a modulating influence on the effects of NA and DA on the impulse activity of the neurons, and that the character of the effect of PG depends on the initial state of the animal.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 6, pp. 1079–1086, November–December, 1989.     

Lack of a role for substance P in the control of dural arterial flow

The role of the neuropeptide substance P (SP) in the control of dural arterial blood flow was examined in barbiturate-anaesthetised rats. The parietal skull was trephinised and the blood flow in branches of the medial meningeal artery was monitored with a laser Doppler flowmeter. Electrical stimulation of the dura mater encephali at a parasagittal site with pulses of 0.5 ms (10–20 V, 5–10 Hz, 30 s) caused a transient increase in dural blood flow which was reproducible in size with repetitive stimulation. Neither the basal flow nor the stimulus-evoked flow was significantly changed by topical administration of SP, the SP analog septide, or the NK₁ antagonist RP 67580. It is concluded that SP released from dural nerve fibres upon local stimulation does not play an important role in the regulation of dural arterial flow.     

Cascade afteraction of delta sleep-inducing peptide in rats

Delta sleep-inducing peptide is found to alter markedly the levels of substance P, β-endorphin, and corticosterone in the hypothalamus and blood plasma of rats, suggesting that the long-lasting stress-mitigating effects of this peptide are due to the considerable changes it causes in the content of other oligopeptides and hormones, involving them in various processes. Thus, DSIP itself appears to act only as a trigger, initiating a cascade of interdependent molecular reactions that correlate with the degree of resistance to stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 6–9, January, 1995     

Hemodynamics in emotional responses and in emotional stress

In the article, we present experimental data indicating that negative emotional states evoked by electrical stimulation of the ventromedial hypothalamus or by behavioral conflicts are accompanied by a predominance of vascular responses of a presser character possessing the property of summation. In contrast, positive emotional states during a self-stimulation reaction or when animals attain behavioral results satisfying their major biological demands are accompanied by a predominance of pressor-depressor vascular reactions. In individual animals under conditions of experimental emotional stress in conflicting situations of a prolonged character, pronounced disturbances of cardiac-vascular functions occur. Predominantly pressor vascular reactions arise in response to forced stimulation of the ventromedial hypothalamus in such cases. It is shown that changes in vascular tonus plays a leading role in disturbances of AP regulation during stress of immobilization. The most frequent cause of death in animals under such conditions is a progressive fall of AP due to an abrupt decrease in the total peripheral resistance. The resistance of the cardiac-vascular functions to emotional stress is determined to a significant degree by genetic mechanisms.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 74, No. 11, pp. 1535–1545, November, 1988.