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Biogenic amines are key mediators of neuroimmune interaction and may influence on multiple sclerosis (MS) pathogenesis and MS course. At the same time, the role of biogenic amines in immunoregulation of early stages of demyelination, in particular clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) is still unclear. This literature review addresses a role of norepinephrine in the regulation of neuroimmune interactions in the early stages of the demyelination. Neuropsychological disorders, immunological characteristics, gut-brain axis as well as the role of norepinephrine in these interactions in patients with CIS, RIS and early MS are discussed.

Aim: To investigate serotonin and catecholamine levels in people with paraphilic disorders and identify correlations between transmitter dysfunction and clinical signs of paraphilic disorders., Material and Methods: Fifteen men with paraphilic disorders were studied using clinical-psychopathological, sexological, biochemical and statistical methods., Results: There were an increase in the levels of serotonin and norepinephrine and a decrease in the concentration of DOPAC (3,4-dihydroxyphenylacetic acid) in the urine of patients with paraphilic disorders. The concentrations of serotonin and norepinephrine are correlated with obsessive disturbances. The level of DOPAC was associated with affective and dissociative disorders., Conclusion: The relationships between biochemical and psychopathological signs suggest a role of biological mechanisms in the organization of abnormal sexual behavior. Correlations between psychopathological phenomena and DOPAC indicate a key role of central dopamine in the pathogenesis of paraphilic disorders and disturbances of conscious regulation of behavior.

The article provides an overview of the literature that focuses on the main types of human adaptation to cold and mechanisms for increasing heat production. It is shown that the studies in recent years, aimed at studying the molecular mechanisms of adaptation to cold, confirmed the results of previous physiological studies have demonstrated that the major contribution to adaptive thermogenesis during cooling made by oxidative fibers in skeletal muscle (birds, marsupials, large placental and people) and brown adipose tissue (small placenta, especially rodents). The main sources of thermoregulatory heat generation are the contractile activity (thermoregulatory shivering and muscle tone), the uncoupling of oxidative phosphorylation and decrease in thermodynamic efficiency of the ATP-powered pumps (ATPase), which are induced by noradrenaline and thyroid hormones and accompanied by an increase in the consumption of oxygen and energy substrates. During long-term adaptation to cold the number and activity of mitochondria increase to provide enhanced ATP consumption.

In this review article, the authors consider a role of interaction between noradrenergic and dopaminergic systems in children with hyperkinetic disorder without impairment of the operational system of intelligence. The uneven development of higher mental functions observed in these cases is determined by the specificity of the formation of functional systems and the inclusion of compensatory mechanisms as well.

The goal of the present study was to verify our hypothesis of humoral interaction between the norepinephrine secreting organs in the perinatal period of ontogenesis that is aimed at the sustaining of physiologically active concentration of norepinephrine in blood. The objects of the study were the transitory organs, such as brain, organ of Zuckerkandl, and adrenals, the permanent endocrine organ of rats that releases norepinephrine into the bloodstream. To reach this goal, we assessed the adrenal secretory activity (norepinephrine level) and activity of the Zuckerkandl’s organ under the conditions of destructed noradrenergic neurons of brain caused by (1) their selective death induced by introduction of a hybrid molecular complex, which consisted of antibodies against dopamine-β-hydroxylase (DBH) conjugated with saporin cytotoxin (anti-DBH-saporin) into the lateral brain ventricles of neonatal rats; and (2) microsurgical in utero destruction of embryo’s brain (in utero encephalectomy). It was observed that 72 h after either pharmacological or microsurgical norepinephrine synthesis deprivation in the newborn rat’s brain, the level of norepinephrine was increased in adrenals and, conversely, decreased in the Zuckerkandl’s organ. Therefore, the experiments with models of chronical inhibition of norepinephrine synthesis in prenatal and early postnatal rat’s brain revealed changes in the secretory activity of peripheral norepinephrine sources. This, apparently, favors the sustaining of physiologically active norepinephrine level in the bloodstream.

The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

The influence of perspective anti-migraine drug tropoxin on the content of monoamines and related metabolites in Wistar rat brain structures, including frontal cortex (FC), hypothalamus, nucleus accumbens (NA), striatum, and hippocampus, has been studied using HPLC/ED technique. Tropoxin (10 mg/kg) induced a 30% decrease (p < 0.05) in dopamine (DA) level in FC as well as norepinephrine content in NA, while the concentrations of DA metabolites DOPAC and HVA in the hypothalamus were found to increase. The injection of tropoxin in a dose of 20 mg/kg led to an increase in HVA level in hypothalamus as well as seroto- nin metabolite 5-HIAA content in NA. The obtained data provide evidence that tropoxin predominantly influenced the activity of dopaminergic system while the drug effects on the parameters of serotoninergic link seem to be rather mild.

It was persuasively shown that norepinephrine released from sympathetic nervous endings plays an important role in the adaptation to cold and epinephrine secreted by adrenal medulla. After acclimatization calorigenic effect of norepinephrine is enhanced. Catecholamines stimulate nonshivering thermogenesis in brown adipose tissue and apparently in white adipose tissue and in skeletal muscles. Adrenergic enhancement of tolerance to cold is depended upon an increase in UCP expression in tissues. In realization of calorigenic effect of catecholamines during long-term cold exposures it is participated following signaling pathway: catecholamines --> β-adrenergic receptors (AR) --> adenylyl cyclase --> cAMP --> protein kinase A --> p38 kinase --> transcription factors --> enhancement of UCP expression. At acute cold exposure it was realized catecholamines --> β-AR --> adenylyl cyclase --> cAMP --> protein kinase A --> hormone sensitive lipase --> free fatty acids --> UCP --> uncoupling oxidative phosphorylation. Calorigenic effect of α1--AR stimulation is realized by following mechanism: norepinephrine --> α1-AR --> phospolipase C --> inositol 1,4,5-triphosphate -->[Ca2+]i --> enhancement of calorigenic effect of catecholamines.

The aim of the work was to study the dependence of individual radiosensitivity of white and black rats on radiation. The rats under study were derived from a cross between black and white rats and called Ratus Ratus-Georgia. Comparative radiosensitivity of white (Wistar) and black rats was studied at a total exposure with sublethal and lethal doses (5, 7 and 9 Gy). Cumulative survival functions of rats, a spectrum of changes in some ethological parameters and content of serotonin and catecholamines in their brain structures were given as criteria of radiosensitivity. Survival rate of black and white rats is connected with changes in the composition and distribution of biogenic amines in the various brain structures, as well as with a decrease of locomotor and orienting-exploratory activity, on the one hand, and with increase of emotionality, stereotyped activity, passive defensive behavior of the rats, on another. Regression coefficients of dependence of survival functions on irradiation doses of black rats were rather higher than those of white rats after irradiation with doses in 5, 7 and 9 Gy. A change in the intensity of mortality with changes in radiation dose per unit depends on the synthesis of serotonin and on the number of sulfhydryl groups, deficiency of which is one of the important factors for white rats. Results of the study allow us to suppose that changes in the radiation sensitivity of rats after irradiation with sublethal and lethal doses are caused by consequences of radiation damage and by activation of the serotonergic system at the process of restitution after radiation injury. On the other hand, a higher radiation sensitivity of white rats in comparison with that of black rats is caused by low content of serotonin, thiols, melanin and other biologically active substances which are endogenous radioprotectors defining individual radioresistance.

The research of the effect of blockade of opioid receptors of the brain in Yakut hibernating ground squirrels (n = 42) by naloxone was performed on animal behavior in the open field and in the hole board during the autumn--period of preparation to hibernation and in spring after arousal (or after the hibernating bout). It is shown that the inhibitory effects of the blockade of opioid receptor on the system parameters total level of activation of the CNS of ground squirrels are more pronounced in autumn than in spring. The results of the biochemical analysis of the levels of monoamines demonstrated a difference in the ratio of noradrenaline/serotonin in the brain of animals in the spring and autumn periods. It is assumed that the interaction of opioid and monoaminergic systems allows, among other factors, to translate homeostasis of hibernating animals on the new level, which necessary for preparation for hibernation in the autumn, as well as, for transition to the active homoiothermic state in the spring.

The influence of corticosterone during the period of tyrosine hydroxylase gene expression (16th-18th days of rat embryogenesis), which is sensitive to hormonal induction, on the ontogenesis of presynaptic markers of the noradrenergic system has been studied. It has been found that hormone-induced changes in the level of noradrenaline and dopamine in the brain cortex and brainstem had a transitive character and were eliminated in adulthood. At the same time, the hormone increased the activity oftyrosine hydroxylase in the cortex of 7- to 16-day-old rat pups and in the cortex and brainstem of adult animals. It has been shown that the level of glucocorticoids is an important factor in development of the noradrenergic system of the brain, able during critical periods of ontogenesis to cause sustained changes of its functioning in subsequent periods of life.

Behavior in the light-dark choice, open-field, sucrose consumption/preference and forced swimming tests, monoamines and their metabolites level in 6 brain structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus, hippocampus, amygdala), and density of D2-like dopamine receptors in 21 brain regions were studied in WAG/Rij and Wistar rats. WAG/Rij rats exhibited symptoms of depression-like behavior such as increased immobility in the forced swim test and decreased sucrose consumption/preference (anhedonia). Substantial changes in behavior indicating increased anxiety in WAG/Rij rats were not revealed. Neurochemical abnormalities suggesting hypofunction of the mesolimbic dopaminergic brain system were found in "depressive" WAG/Rij rats compared with "normal" Wistar rats: decreased levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine in the nucleus accumbens, and increased density of D2-like dopamine receptors in the nucleus accumbens and ventral tegmental area. Reduced levels of dopamine were also observed in the prefrontal cortex and striatum. No substantial changes in the content of monoamines and their metabolites have been revealed in the hypothalamus, hippocampus and amygdala as well as in the content ofserotonin and its metabolite 5-hydroxyindolacetic acid in all studied brain structures with the exception of increased level ofserotonin in the amygdala. Results suggest that hypofunction of the mesolimbic dopaminergic brain system (nucleus accumbens) is a neurochemical mechanism of depression-like behavior in WAG/Rij rats.

Among most important functions of the neuroendocrine system is the regulation of reproduction, including the inhibitory control of prolactin secretion by dopamine (DA) synthesized in the arcuate nucleus (AN). Besides DA, noradrenaline (NA) contributes to this regulation though, in contrast DA, its concrete functional role remains to be uncertain. In the previous studies, it has been suggested that NA inhibits compensatory synthesis of DA in DA-producing neurons of AN under the failure of the dopaminergic system though no evidence were obtained. Therefore, the goal of this study was to specify the role of NA in the regulation of DA-producing neurons in AN. Two pharmacological models were used to this aim: a) switching off dopaminergic and noradrenergic neurons and their afferents in An or b) switching of only dopaminergic neurons and afferents that allowed us to recognize NA role in the complex catecholaminergic regulation of prolactin secretion. According to our data, the maintaining of the noradrenergic innervation of AN under the neurotoxin-induced failure of dopaminergic neurons resulted in the decrease of the expression of tyrosine hydroxylase (TH), the first enzyme ofDA synthesis, thereby enhancing DA deficit. This is considered as direct evidence of noradrenergic inhibitory control of TH expression in the neurons of AN.

Possible involvement ofcalmodulin in adrenergic and serotoninergic regulation of vascular contractility has been studied. Calmodulin inhibitors trifluoperazine and W-13 suppress vasoconstriction of the rat aorta in response to norepinephrine, serotonin, and serotonin 5HT1A- and 5HT2A-receptor agonists (8-OH-DPAT and DOI, respectively) and do not affect the vasodilatory effect of 5HT1B-, 5HT2B-, and 5HT4-receptors. The force of aorta contraction in response to 8-OH-DPAT increases after the activation of calcium entry through voltage-gated Ca2+-channels. This effect is not related to non-specific activation of alpha1-adrenoceptors, since it is realized in the presence of prazosin. The inhibitor of calmodulin-dependent myosin light chain kinase KN93 decreases the vasoconstrictive response in response to norepinephrine and serotonin by only 20%. Calmodulin inhibitors slightly decrease aortic constriction in response to endothelin-1, vasopressin, angiotensin II, and KCl. Trifluoperazine does not suppress vasoconstriction induced by the G-protein activator AlF4(-). It is assumed that the target of trifluoperazine and W-13 is calmodulin interacting directly with alpha1-adrenoceptors and serotonin 5HT1A- and 5HT2A-receptors.

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

To elucidate disorders of psychoneurohumoral relationships in patients with grade I-II arterial hypertension at low, moderate and high overall cardiovascular risk, we measured body mass index, activity of sympathetic nervous system, serum leptin level and performed psychological tests aimed to elucidate situational and personal anxiety, aggressiveness and hostility. The data obtained allow a patient to be referred to one of the three possible types of disturbed psychoneurohumoral interrelations, viz. anxiety-metabolic, anxiety-adrenergic, and aggressive-metabolic, each having its own specific gender-related and clinical features. Discrimination between these types permits to substantiate pathogenetic therapy of arterial hypertension on an individual basis.

Effects of GB-115, an anxiolytic L-triptophan-containing dipeptide, based on the endogenous tetrapeptide cholecystokinin, were evaluated during and after withdrawal of its long-term administration to rats in comparison with diazepam. It was shown using the "elevated plus-maze" test (EPM) that GB-115 retained its anxiolytic properties after i/p injections at a daily dose of 0.1 mg/kg fo r 30-days. Discontinuation of dipeptide administration 24h and 48 hours after the onset of the experiment did not lead to behavioral (increased anxiety, aggression) and convulsive (decreased corazol sensitivity) manifestations of withdrawal syndrome. In contrast, the withdrawal ofdiazepam (4.0 mg/kg/day, ip, 30 days) induced the anxiogenic response in EPM, reduction of the aggression threshold, and enhancement of convulsive readiness. Significant differences between GB-115 and diazepam effects on the levels of dopamine, norepinephrine, and their metabolites after chronic administration and withdrawal were restricted to striatum.

Proliferation of Saccharomyces cerevisiae EPF cells on solid maltose-peptone-yeast extract (MPY) medium was stimulated by the addition of monoamine neurotransmitters. Dopamine turned out to be the most efficient among them: it caused approximately 8-fold growth stimulation at 1 microM concentration. The dopamine effect was partly mimicked by apomorphine, a dopamine receptor agonist. Serotonin and histamine produced less significant (1.5-2-fold) effects, and norepinephrine virtually failed to stimulate yeast culture growth. These data point to a specific, apparently receptor-dependent mode of action of the tested neurotransmitters on S. cerevisiae cells. Using high efficiency liquid chromatography, serotonin, catecholamines (dopamine and norepinephrine), catecholamines precursor dioxyphenylamine, and oxidized amine products (homovanilic acid, dihydrophenylacetic acid, and 5-hydroxyindolacetic acid) were established to be accumulated in yeast cells up to (sub)micromolar concentrations without their release into the culture fluid supernatant (CSF). The results obtained suggest that the tested amine neurotransmitters and related compounds do not serve as autoregulators in the yeast population. Nevertheless, they may be involved in the regulation of yeast population development by other ecosystem components.

The aim of this work was to evaluate the hypothesis that the second-generation antidepressant, might play a role in controlling the activity of noradrenalergic neurotransmitters. The paper details the pharmacological profile of antidepressant drug Fluoxetive with high affinity for 5-HT receptor, and explains how the antidepressant activity chances noradrenalin reuptake inhibitor-medications. Brain cortexes of 20 rabbits were analyzed by high-performance liquid chromatography. The conducted quantitative and qualitative analyzes show that antidepressant activity of Fluoxetine could be mediated by the synergistic effects on the serotoninergic and noradrenergic receptor pathways. Major depressive disorders are heterogeneous monoamine condition. Our studies have demonstrated fluoxetine efficacy and safety for treatment of major depressive disorders.

The present review describes the diagnostic value of the metabolites of epinephrine, norepinephrine, dopamine, and serotonin in the laboratory diagnosis of drug abuse. The metabolism and effects of these substances in health and drug addiction are considered. A procedure for their analysis is presented.

To determine the effect of uptake 1 inhibition in reperfusion after myocardial ischcmia upon noradrenalin dynamic and myocardial infarction size, 14 male Wistar rats anesthetized with urethane were randomly divided into 2 groups and subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. In control group (n = 7) 1 ml of Ringer's solution was administered intravenously at the beginning of reperfusion. In experimental group (n = 7) instead of Ringer's solution 0.8 mg/kg of desipramine was used. Myocardial interstitial noradrenalin levels were measured using a microdialysis technique. Infarction size was determined by triphenyltetrazolium chloride staining and was related to the area at risk. Desipramine increased infraction size from 32.0 +/- 3.1 % (control group) to 46.1 +/- 3.4% (p = 0.06). Interstitial noradrenalin in experimental group did not decrease during 120 min reperfusion (p < 0.05 vs. control). The data obtained suggest that uptake 1 inhibition in reperfusion after myocardial ischemia increases myocardial infarction size through increased interstitial noradrenalin.

We implanted under urethane narcosis microdialysis probes into myocardium of Wistar rats. In experimental group we used ischemic preconditioning. After this left descending coronary artery was occluded for 60 minutes and then reperfused for 60 min. In control group prolonged occlusion was preceded by 30 min of rest. Significant elevation of noradrenaline concentration in myocardial interstitium was noted at 20th and 10th minutes of testing ischemia in experimental and control groups respectively. From 20th minute to the termination of occlusion noradrenaline concentration in myocardial in animals of control group was significantly higher than that in preconditioned animals. Concentration of dihydroxyphenylglycol in interstitium reflecting noradrenaline metabolism in axoplasm fell during ischemia and rose when reperfusion was started. Elevation of dihydroxyphenylglycol was statistically significant compared with both baseline level and control (p<0.005) practically at all stages of reperfusion. Thus ischemic preconditioning inhibits effectively noradrenaline accumulation in myocardial interstitium during prolonged ischemia. After ischemic preconditioning normal mechanism of noradrenaline reuptake functions longer however because of impaired storage in vesicles substantial part of noradrenaline remains in free state in axoplasm to be subjected to deamination with participation of monoamine oxidase.

The aim of this review was to summarize the literature data, which characterize the participation of brain noradrenergic system and sex steroids in the regulation/modulation of amygdala functions. Structural organization of noradrenergic system and its representation in corticomedial and basolateral divisions of amygdala is described. This is important for further development of the understanding of the heterogeneity and structural organization complexity of the amygdale, which possesses functional multiplicity. The evidence is presented that may help in comprehension of the influence of gender factor on human personality characteristics, cognitive abilities and behavioral reactions. These data may also be applied for development of optimal clinical medicinal treatment of psychoneurological diseases.

Levels of dopamine (DOPA), noradrenalin (NA), and serotonin in hypothalamus and function of ovaries (folliculogenesis) were studied at various estrous cycle stages of the rat GK line selected for elevated catatonia. The control was the outbred Wistar line. Selection for elevated catatonia led to a decrease of the number of all cell types in GK ovaries in diestrus and proestrus. In estrus of the GK females, on the contrary, there was a tendency for an increase of the number of the growing follicles as compared with Wistar females. On the background of a decrease of the DOPA and NA content in hypothalamus of the GK line rats, the higher catecholamine level was observed in estrus and the lower--in diestrus. Thus, selection for manifestation of the excessive protective catatonical type of reaction in the form of an increase of duration and intensity of freezing involves the monoaminergic brain system and leads to delay of folliculogenesis that is the key factor in regulation of fertility.

The goal of this work was to study possible mechanisms underlying the potentiation of vasopressor response to serotonin observed in traumatic shock. Experiments with isolated aorta and mesenteric artery of the rat showed that vasoconstriction is caused by the activation of 5HT2A receptors. Agonists of 5HT1B, 5HT1D, 5HT2B, and 5HT4 receptors induced vasodilation. Agonists of 5HT1A receptors had a dual effect determined by interaction with alpha1-adrenergic receptors and 5HT1A receptors. Plasma membrane depolarization with 15 mM KCl increased the vasoconstrictive force in response to serotonin. This effect was determined by the ability of KCl to activate voltage-gated calcium channels, as a result of which the intracellular calcium stores are replenished. Inhibition of serotonin response by ketanserin, a 5HT2A receptor blocker, did not depend on the presence of 15 mM KCl. Constriction in response to serotonin was potentiated after its addition to vessels preconstricted with noradrenaline or endothelin-1. The constriction response partially retained in the presence of 2 x 10(-7) M ketanserin, which completely suppressed the serotonin-induced constriction of dilated vessels both at normal membrane potential and after plasma membrane depolarization. It can be assumed that noradrenalin and endothelin-1 alter the characteristics of 5HT2A receptors and possibly 5HT1A receptors as a result of their heterodimerization with the receptors for these vasoconstrictive hormones or interreceptor interaction at the level of signaling systems. Along with the potentiating effect of KCl, this mechanism may underlie the enhancement of vasopressor response to serotonin in shock.

Lipid and phospholipids content of heart, vagus nerve, stellate ganglion tissues, erythrocytes and blood plasma from rabbits of different age groups were investigated. Older animals with effect of serotoninergic nerve potentiation of vagal hampering of a heart are characterized by higher concentration of cholin-containing phospholipids, by larger cell membrane permeability.

A long-term (21 days) administration of the specific bradycardic agent zatebradine to rats with experimental myocardial infarction led to a decrease in the intensity of necrotic changes in the cardiac muscle as evaluated from the ECG-recorded QS complex incidence rate. Morphological studies provided evidence for reduced intensity of the dystrophic processes in myocardium. Under these conditions, the drug did not affect the pump and contractile heart functions. At the same time, zatebradine normalized the reaction of mean aorta blood flow acceleration to volume load (which was inhibited at myocardial infarction), that is, prevented the development of latent heart failure. Zatebradine restored the infarction-decreased norepinephrine (NE) level in cardiac muscle and increased NE content in hypothalamus and brainstem. Along with that, the ratios of deoxyphenylacetic acid/dopamine and homovanillic acid/dopamine were reduced.

Existing data on hippocampal involvement in contextual memory and the fact that contextual memory is deranged during REM sleep dreams allowed us to assume that one of the reasons for this derangement could be a change in the efficacy of synaptic transmission in the hippocampus because of a rise (as compared to wakefulness) of acetylcholine, cortisol, and dopamine concentrations and lack of serotonin and norepinephrine. The earlier performed analysis showed that, during REM sleep, the LTD could be induced at all steps of the polysynaptic pathway through the hippocampal formation, whereas the LTP could be induced in the entorhinal inputs to hippocampal areas CA1 and CA3 and in associative connections within the CA3 field. We suggested that the effective signal transmission in each units of the polysynaptic pathway through the hippocampus is necessary for correct functioning of episodic memory and generation of neuronal representation of the context. During retrieval in the state of wakefulness, the representation of episodic context stored in the hippocampus could be activated together with the neuronal representations of episodic details stored in those neocortical areas wherein they were processed. It follows from the proposed mechanism that any neuromodulator or neuropeptide which promotes LTP in the polysynaptic hippocampal pathway can improve episodic memory. Since the consequences of the proposed mechanism agree with the known experimental data, this phenomenon can be used for the development of drugs improving episodic memory.

Weights of the body, ovaries, and uterus; estrous cycles and the contents of dopamine (DA) and norepinephrine (NE) in the hypothalami, and testosterone in blood plasma of GC females were studied at various estrous stages (diestrus and estrus). The outbred Wistar line was used as a control. In addition to reduced body weight in GC females, we observed disturbed morphological cyclic linkages between the ovaries and uterus: ovary weight reduction in diestrus (p < 0.01) and lower estrogen-related increase in uterus weight in estrus in GC females in comparison with Wistar ones. While the contents of DA and NE in GC hypothalami were reduced, the levels of these monoamines were high in estrus and low in diestrus. Testosterone levels in GC female plasma in diestrus were higher than in estrus or in Wistar rats.

Aim of the Study: To determine the effects of two-staged ischemic preconditioning on myocardial noradrenaline in prolonged ischemia and reperfusion., Methods: Thirty-two male Wistar rats anesthetised with urethane randomly divided into 2 groups: group 1 (ischemic preconditioning group, n = 16), and group 2 (control, n = 16). Myocardial interstitial noradrenaline levels were measured using a microdialysis technique. Ischemic preconditioning was elicited by two episodes: 5 min of ischemia and 10 min of reperfusion. The intermittent occlusions were followed by prolonged occlusion (60 min) and reperfusion (60 min)., Results: An increase in interstitial noradrenaline was observed in 10 min of prolonged ischemia in group 2, and in 20 min in group 1. After 20 min of myocardial ischemia there was a significant difference between groups (p < 0.05) in interstitial noradrenaline levels. In control group, it was 60% higher. In reperfusion, noradrenaline levels decreased markedly in group 1., Conclusion: We suggest that ischemic preconditioning by two episodes: 5-min ischemia and 10-min reperfusion prevents excessive noradrenaline interstitial accumulation, perhaps, through protection of physiological uptake I carrier.

It has been shown that the peptide anxiolytic drug Selank recovers learning and memory impaired by damage of the noradrenergic (NA) brain system in Wistar rats after injection of the NA-synthesis inhibitor disulfiram, administration of neurotoxic compound 6-OHDA, or a combined induction of hypoxic hypoxia and hypercapnia. The main component of the Selank action is the stimulation of the search reflex aimed to distinguish an adequate adaptive response in the first trials of the learning session. The enhancement of memory consolidation and retrieval shows evidence for stimulation of the brain motivation mechanisms impaired by the NA system damage.

Salt-loading in adult mammals stimulates vasopressin secretion by vasopressinergic neurons of the supraoptic nucleus that is under control by a number of hormones and neurotransmitters including noradrenalin. This study was aimed to determine at what period of ontogenesis the vasopressinergic neurons begin to respond to salt-loading and when the noradrenergic control of this process is switched on. Rats on the 21st embryonic day (E), the 3rd postnatal day (P) and P13 were salt-loaded, sometimes under simultaneous treatment with prasozin, an inhibitor of al -adrenoreceptors. Thereafter, the hypothalamic nuclei of the animals were processed for immunocytochemistry and in situ hybridization. Salt-loading provoked increased synthesis of vasopressin mRNA and, most probably, vasopressin itself in rats in all studied age groups. Under salt-loading, the intraneuronal content of vasopressin increased significantly at E21 and P3, whereas it did not change at P13. No change in the intracellular contents of vasopressin mRNA and vasopressin was observed in foetuses following salt-loading and treatment with prasozin though the same treatment provoked an increase of both parameters at P3. These data show that noradrenalin provides an inhibitory control of vasopressin expression at least since P3. Thus, vasopressinergic neurons begin to respond to salt-loading at the since P3. Thus, life by the increased expression of vasopressin that is postnatally under the inhibitory control by noradrenalin.

Character of tissue changes as well as their reversibility could vary depending on the duration of myocardial ischemia. Long (over 30 min) ischemia leads to a massive release of myocardial interstitial norepinephrine. We tried to investigate changes in the myocardial sympathetic system produced by a relatively long episode of ischemia-repeperfusion. Myocardial norepinephrine has been collected by means of microdialysis probe during repeated occlusions of the left descending coronary artery. It was shown that long episode of occulusion-reperfusion resulted in suppression of massive norepinephrine release in response to second (test) occlusion. The features of norepinephrine release during successive occlusions make it possible to associate this process with the reversibility of the ischemic tissue damages.

Typological characteristics of behavior were studied in rats bred for enhancement (PM+) and absence (PM-) of pendulum movements. Excitement in different test situations was manifest in PM+ rats, whereas passive defensive reactions were characteristic of PM- rats. Increased excitability of PM+ rats was expressed in their greater predisposition to audiogenic epilepsy (83% in PM+ versus 40% in PM- rats). On the contrary, PM- rats were found to be more prone to freezing (61% in PV- versus 11% in PM+). In PM+ rats, noradrenaline and serotonin contents were decreased in hypothalamus (as compared to PM- and control Wistar stain), whereas in PM- rats, serotonin content was increased in striatum, hypothalamus and midbrain as compared to control strains.

The effects of hydrocortisone acetate treatment of rats during the last gestational week on neurochemical and morphological characteristics of the brain in early postnatal and mature offspring were studied. Disappearance of sexual differences both in aromatase and 5alpha-reductase activities and noradrenaline concentration in the preoptic area in 10-day old rats was found. Meanwhile a sexual dimorphism in serotonin metabolism emerged. In adult offspring, the prenatal exposure to glucocorticoids resulted in disappearance of sexual differences in neurocytes' nuclei volume in medial preoptic and suprachiasmatic nuclei. The adrenocortical reaction to noradrenaline infusion to the 3rd brain ventricle was absent in the experimental males and intensified in females. In males, adrenocortical reaction to restraint decreased while post-stress changes in hypothalamic noradrenaline concentration and hippocampal glutamate decarboxylase activity were not observed. In the similar experiments in females both the augmentation of adrenocortical reaction and inhibition of GABA-ergic system were revealed. The results obtained indicate the modifying effect of prenatal exposure to glucocorticoids on sexual dimorphism of neuroendocrine system.

The paper presents recent clinical data on usage of pronoran, a dopaminergic and noradrenergic medication, in the treatment of mild and moderate cognitive impairment in elderly. Efficacy of pronoran was shown in a number of placebo-controlled as well as open clinical trials including those carried out in Russia. Presented are also the results of the large-scale study PROMETEY which has been performed in Russia in 2004-2005. The study revealed that 70% of elderly neurological patients had cognitive impairment. Pronoran was included in the treatment of cognitive impairment in the frames of this study and showed a marked therapeutic effect in 82% cases.

The data obtained in our experiments concerning the effect of long-tern adaptation to cold and noradrenaline on impulse activity of the central hypothalamic and peripheral skin thermoreceptors, are reviewed. The problems of sympathetic system participator in cold adaptive modifications and importance of thermoreceptors in formation of cold-defense responses, as well as the role of different types of thermoreceptors in thermal sensation, are discussed.

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

Effects of serotonin uptake inhibitor fluoxetine (F) and it's complexes with glycyrrizhinic acid (GA) in molar proportions 1GA : 1F (FGA-1) and 4GA : 1F (FGA-4) on rat behavior in elevated plus-maze and brain monoamine concentrations were studied. Drugs (25 mg/kg) were administered per os 1 h before investigations. F-treated rats showed increased anxiety and reduced locomotor activity, whereas FGA-1 and FGA-4 had no effects on the behaviors. None of the compounds modified brain tissue serotonin content, but all of them decreased the level of its metabolite 5-hydroxyindole-3-acetic acid level in the hypothalamus, and FGA-4 also decreased it in the cortex. Noradrenaline levels were increased in the hypothalamus of rats treated with F in both combinations with GA. In the striatum, F increased dopamine and its metabolite DOPAC levels, but their ratio (an indicator of the neurotransmitter turnover) was not altered by this drug. Unlike F, FGA-1 significantly activated dopamine turnover in the striatum. The data obtained suggested that application of F in complexes with GA significantly modified the drug behavioral effects and these alterations may be related to specific effects of the pure compound and its complexes on the functions of the brain monoaminergic systems that regulate investigated behavior.

Aim: To compare effects of various regimens of long-term monotherapy with quinapril (an ACE inhibitor) and valsartan (a type 1 angiotensin II receptors blocker) and combined therapy with these drugs on the activity of heurohormonal systems and 24-h heart rate variability (HRV) in patients with stable moderate chronic cardiac failure (CCF)., Material and Methods: A total of 80 patients with FC II-III CCF secondary to coronary heart disease (CHD), delated cardiomyopathy (DCMP) and decompensated hypertensive heart (49%/47%/4%) were randomized into 3 groups. Group 1 patients (n = 28) received quinapril, group 2 (n = 26)--valsartan, group 3 (n = 26)--quinapril + valsartan. The levels of norepinephrine (NE), angiotensin II (AT II), activity of plasmic renin (PR), aldosteron (AS), plasmic cerebral sodiumuretic peptide (CSUP) were measured and ECG with determination of HRV and heart rate disturbances was made before and 3, 6 months after the treatment., Results: NE concentration lowered most significantly in group 1 (from 630 to 405 pg/ml) vs groups 2 and 3 (from 525 to 490 pg/ml and from 525 to 480 pg/ml, respectively). A 6-month treatment induced significant changes neither in concentrations of AT II nor AC. ATII concentrations rose 2-fold in group III (from 11.9 to 24.3 pg/ml) under a parallel rise of PR activity from 0.7 to 2.5 ng/ml/h and a fall in AS level from 132 to 83 pg/ml. In group 2 AS diminished also (from 165 to 126 pg/ml). CSUP decreased in all the groups, but significantly only in groups II and III (from 350 to 237 and 322 to 204 pg/ml after 6 months of treatment, respectively). Significant changes of 24-h HRV (both spectral and temporary) were observed in group 1 after 3 months of treatment. These changes lost significance to the end of the treatment. In groups 2 and 3 the changes were less pronounced., Conclusion: Quinapril is more potent than valsartan and quinapril + valsartan combination in relation to activity of sympathico-adrenal system and HRV in patients with moderate stable CCF. Long-term therapy with valsartan does not improve parameters of HRV in moderate CCF. If CCF patients take quinapril for a long time, they develop the effect of disappearing block of AS synthesis and reactivation of A TII production. The best mechanism of long-term control over the activity of renin-angiotensin-aldosteron system in patients with moderate CCF is combination of quinapril with valsartan.

The authors of the article analyze the dynamics of the myocardial pumping ability after surgical repair of congenital and acquired heart valvular diseases. Measurement of the intracardial and central hemodynamics allowed the authors to demonstrate the significance of the diastolic component of heart functioning and the subendocardial circulation condition in the development of preclinical heart failure. The study shows a clear interrelation between myocardial functional load and increase of catecholamine concentration in it. An abrupt fall of norepinephrine concentration in the myocardium suggests an extreme overload of the sympathico-adrenal system and its exhaustion, caused by extremal functioning conditions.

This review describes a role of stress in formation of the primary drug-taking behaviour and the effects of stress on a drug-seeking behaviour after withdrawal of drugs. The psychophysiological and neurochemical mechanisms of the rewarding and aversive states during a drug taking and after its withdrawal are considered. A role of separate neurotransmitters and their interactions in formation of drug dependence and the effects of stress on neuroadaptive changes in these neurotransmitter systems are described. A review of the structures involved in mediation of the stress effects and a drug-seeking behaviour is also discussed.

Seasonal features of open-field behavior of Yakut ground squirrels (Citellus undulatus) and changes in the brain MAO A activity were studied. It was found that all parameters of exploratory activity in the open field and holeboard test reached the values characteristic of summer animals very rapidly, within a few days or (in some cases) even within the first 24 hours after the arousal from hibernation in the middle of April. In autumn these parameters decreased to their minimum values 1.5-2 months prior to hibernation. Biochemical analysis showed that in April the activity of MAO A measured with serotonin as a substrate in the hippocampus was 1.8 times (p < 0.05) higher than the activity of MAO A with respect to noradrenaline. In contrast, in autumn the MAO A activity determined with noradrenaline as a substrate was 2.5 (p < 0.05) times higher than the activity a MAO A with respect to serotonin. Taken together, these data indicate that the seasonal features of the higher nervous activity of hibernating animals depend on the balance between serotonergic and noradrenergic systems in different periods of the annual cycle.

Hibernation (winter sleep) is a kind of unique adaptive behavior of small mammals subjected to fine and complex central control. One of the most promising approaches to this problem is a search for the mechanisms providing brain control under conditions of a sharp decrease in temperature, (virtually, to zero) and metabolic rate. Studies conducted at the Laboratory of System Organization of Neurons under the supervision of Professor O.S. Vinogradova confirmed the hypothesis of the special role of the septohippocampal system in the control of winter sleep. Together with a brief characterization of hibernation in general, the data obtained at the Laboratory are also summarized in the review. The experimental evidence for the role of the medial septal area as a "sentry post" in hibernation is presented.

The evidence for the role of serotonergic and noradrenergic effects on the septohippocampal theta oscillations obtained by the author and her colleagues are reviewed. Analysis of neuronal activity in the medial septal area or hippocampus and hippocampal EEG simultaneously recorded in awake rabbits exposed to different kinds of brainstem influences led to the following conclusions. 1. Serotonergic median raphe nucleus and noradrenergic locus ceruleus act as functional antagonists in theta regulation: the former structure restricts the theta rhythm generation, whereas the latter enhances this process. 2. Both transmitter systems control sensory reactions of septal and hippocampal neurons through up and down regulation of the theta activity. 3. When continuous theta activity induced by various experimental manipulations is recorded, responsiveness of septohippocampal neurons to sensory stimulation is strongly reduced. These findings provide support for the view that the theta oscillations act as an active filter in the information selection and registration. Interaction of different transmitter systems in the theta rhythm control as well as attention and memory is discussed.

The dynamics of neurotransmitter stage in the development of autonomic nervous system (ANS) was studied in rats starting from the moment of initial appearance of neurotransmitters acetylcholine and adrenalin in ANS peripheral part main nervous plexuses. Cryostat sections of embryos on developmental days 13.5, 16.5 and 18.5 and of neonatal rats aged 0.5 and 1.5 days were treated with glyoxilic acid, using Karnovsky-Roots method and impregnated with silver nitrate according to Bielschowsky-Gross method. Acetylcholinesterase in vagus and in spinal ganglia was found on day 13.5, while catecholamine in sympathetic trunc was detected in animals immediately after the birth. Periods of the beginning of neurotransmitter stage in ANS development in rat and man were compared and it was established that it was delayed in rat as in immature-born animal.

The goal of this work was to find out to which degree the black coat color mutation nonagouti that appears in wild Norway rat in the course of breeding for the maintenance and enhancement of aggressiveness towards a human affects selected and other behavioral traits as well as stress reactivity and brain neurochemistry. Nonagouti rats displayed increased emotionality in the open-field and forced-swimming tests as compared to agouti animals, whereas there were no differences in anxiety estimated in the elevated plus-maze. Neither were there any differences in glucocorticoid reactions to a combined stressful procedure such as forced swimming. The dopamine content in the frontal cortex and striatum and noradrenaline content in the frontal cortex were increased in black rats as compared to gray rats. The result suggest that the nonagouti mutation in gray aggressive rats enhances the effects of selection for aggressiveness on some behavioral traits and brain catecholamine level.

Aim: To study changes in some components of stress-realizing system (SRS) and stress-limiting system (SLS) characterizing compensatory mechanisms in acute disturbance of cerebral circulation (ADCC)., Material and Methods: The activities of SRS and SLS were assessed in 94 patients by changes in the concentrations of glutamate, aspartate, acid phosphatase for SRS and gamma-aminobutyric acid (GABA) for SLS, respectively., Results: After analysis of clinicobiochemical correlations the following clinical phases were singled out: subcompensation, moderate decompensation, severe decompensation and terminal. The phase conversion depended on quantitative changes of SRS and SLS activity. This enabled characterization of severity in certain time periods. Imbalance was revealed between SRS and SLS because of hyperactivation or hypoactivation of one of the above systems., Conclusion: Imbalance between SRS and SLS converts stress-syndrome from nonspecific link of adaptation into a nonspecific link of the disease pathogenesis.