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The seasonal peculiarities of the circadian activity of hibernator, Yakutian long tail ground squirrels (S. undulatus) (n = 35) and non hibernator, Wistar rats (n = 35), were studied. The locomotor activity was registered in each subject individually during 5-17 days by means of "Animex" in the different periods of annual cycle. It was shown that ground squirrels were animals with daily type of activity. On the contrary, the Wistar rats demonstrated nocturne type of locomotors activity. The active period in rats was longer than in ground squirrels. It included not only at night, but morning time in spring, and daytime--in summer. The circadian differences between hibernators and non-hibernators were kept during all annual cycle at night time, but in daytime--only in spring and summer time.

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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.

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The effect of selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which is a synthetic derivative of the endogenous tetrapeptide tuftsin (stable with respect to tissue peptidases), on the learning and memory processes and metabolism of serotonin (5-HT) have been experimentally studied on Wistar rats. The animals were trained with food reward in 30 trials per day. Selank (300 microg/kg) or saline were injected after the 10th trial. Elaboration of conditioned reflex with food reward was continued 30 min later. Retention was tested 24 h, 7 and 30 days after treatment. A single injection of selank activated the metabolism of 5-HT in the hypothalamus and caudal brain stem for 30 min to 2 h. It was established that selank induces an increase in memory trace stability during 30 days. These findings provide direct evidence that selank, when injected during consolidation phase, can enhance memory storage processes. Nootrope activity of the selank is probably caused by its obvious effect on the level of serotonin and its metabolite in the brain.

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Effects of the peptide drugs selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) and tuftsin (Thr-Lys-Pro-Arg) on the metabolism of serotonin (5-hydroxytryptamine, 5-HT) in the brain of Wistar rats preliminarily treated with the 5-HT-synthesis inhibitor p-chlorophenylalanine (PCPA, 320 mg/kg, i.p., 4 days before experiment) have been studied on a group of 87 matured rats. It is established that selank enhances the 5-HT metabolism in the brain stem 30 min after injection to animals pretreated with PCPA. In contrast to selank, tuftsin induced no changes in the 5-HT metabolism in the brain stem and decreased it in the neocortex on the same time scale. The data obtained suggest that the peptide drug selank can be used for the correction of disturbances induced by a decrease in 5-HT metabolism.

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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.

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The effects of Selank, the active component of which is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro, which includes the tetrapeptide tuftsin and three natural levorotatory amino acids, on behavior and brain serotonin and noradrenaline levels were studied in adult rats subjected to antenatal hypoxia on days 14-16 of gestation. Administration of Selank (300 microg/kg, i.p.) improved sensory attention levels by factors of 2-3 (p < 0.01), facilitated the learning process by a factor of 1.5 (p < 0.01), normalized the level of investigative activity in the open field and hole board, and restored the balance of activity between the serotoninergic and noradrenergic systems of the brain. The data obtained here provide evidence that Selank can be used to compensate for the long-term negative effects of antenatal hypoxia on brain integrative activity and the activity of monoaminergic transmitter systems.

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Hibernation is a unique physiological state characterized by profound reversible sleep-like state, depression in body temperature and metabolism. The serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptor gene sequence in typical seasonal hibernator, ground squirrel (Spermophilus undulatus), was specified. It was found that the fragment encoding the fifth transmembrane domain showed 93.6% of homology with the analogous fragment of the mouse and rat genes and displayed 88.5% homology with the human 5-HT(1A) receptor gene. Using primers designed on the basis of obtained sequence, the expression of 5-HT(1A) receptor gene in the brain regions in active, entering into hibernation, hibernating and coming out of hibernation ground squirrels was investigated. Significant structure-specific changes were revealed in the 5-HT(1A) messenger RNA (mRNA) level in entry into hibernation and in arousal. An increase in the 5-HT(1A) gene expression was found in the hippocampus during the prehibernation period and in ground squirrels coming out of hibernation, thus confirming the idea of the hippocampus trigger role in the hibernation. Significant decrease in 5-HT(1A) receptor mRNA level in the midbrain was found in animals coming out of hibernation. There was no considerable changes in 5-HT(1A) receptor mRNA level in different stages of sleep-wake cycle in the frontal cortex. Despite drastically decreased body temperature in hibernating animals (about 37 degrees C in active and 4-5 degrees C in hibernation), 5-HT(1A) receptor mRNA level in all examined brain regions remained relatively high, suggesting the essential role of this 5-HT receptor subtype in the regulation of hibernation and associated hypothermia.

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Effects of selank on learning, memory, and attention to sensory stimuli of different modality were studied in adult Wistar rats treated with 6-hydroxydopamine (neurotoxin selectively damaging catecholaminergic neurons and their terminals) during the first 3 days of life. Selank (300 microg/kg) restored cognitive processes disordered by chronic artificial inhibition of the cerebral catecholaminergic system.

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The effects of Selank synthetic analog of Tuftsin, representing the heptapeptide forming Thr-Lys-Pro-Arg-Pro-Gly-Pro, on behavior and serotonin/noradrenalin concentrations in brain were investigated in adult rats exposed to hypoxia during 14-16 days of gestation. It was revealed that injection of Selank (300 mkg/kg, i/p) increased 2--3-fold (p < 0.01) the sensory attention, facilitated 1.5-fold the learning capacity (p < 0.01), normalized exploratory activity in the open field and hole board, and recovered the balance of serotonergic and noradrenergic brain system activity. The data obtained demonstrate the possibility of Selank to compensate for long-lasting negative effects of antenatal hypoxia on integrative brain activity and brain monoamine level.

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We studied the seasonal effects of peptide preparation Selank on orientation and exploratory activity in 36 arctic ground squirrels Citellus undulatus in the open-field and hole-board tests. Selank most significantly increased behavioral activity of hibernating animals in the spring and fall. The test peptide had no effect on locomotor activity of animals. The selective stimulatory effect of Selank on exploratory behavior of hibernating animals was season-dependent. The maximum effect was observed under conditions of seasonal depression-like state.

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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.

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The dependence of activities of actomyosin ATPase, alkaline phosphatase, aspartataminotranspherase, monoaminoxidase and that of affective rat behavior on frequency of modulation of microwaves (0.8-10 microW/cm2) was explored at short-time actions. Series of nonlinear phenomenons, inexplicable from positions of the energy approaches are revealed, The working hypothesis explaining opportunity of high performance of weak and super-weak microwaves and other revealed phenomena by resonance interaction of such electromagnetic radiofrequency radiation with paramagnetic molecules of biological tissues was proposed. This resonance interaction activate free radicals and initiate auto-supporting and auto-intensifying of chain chemical reactions. The spontaneous autocatalytic oxidation of catecholamines enlarges a common pool of free radicals, capable to participate in such enhanced generating. The protective role of monoaminoxidase is postulated. Monoaminoxidase is basically located on an outer surface of mitochondrias and it is deaminating monoamines. The deaminating prevents penetration of catecholamines inside of mitochondrias and their quinoid oxidation there with formation of free-radical semi-quinons, capable to destroy system of ATP synthesis. These inferences are obliquely confirmed by the experimentally revealed correlation between activity of monoaminoxidase and integrative activity of the rat brain.

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Seasonal changes in the behavior of ground squirrels Citellus undulatus (n=35) in holeboard and open field tests were studied. It was found that the number of head dips and rearings in the holeboard and the number of crossed squares, rearings, and runs across the field center in the open field in ground squirrels during arousal between bouts at the end of the hibernation period, in the middle of March, were lower than these indices in active summer animals. A rapid restoration of all behavioral parameters after the arousal of animals from hibernation in mid-April was shown. In some cases, the behavioral parameters of activity in the holeboard and open field tests and the habituation reaction reached the values characteristic of active summer animals in a very short period of time, sometime within 1 day. By contrast, the locomotory and exploratory activities of animals tested in autumn (at the beginning of September and in the middle of October) were significantly lower than in summer animals, i.e. these indices decreased to minimum values 1.5-2 months prior to their entry into hibernation. The results of behavioral experiments indicate that the preparation of the CNS of hibernators for seasonal changes in the functional states is under the control of endogenous regulators.

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The effects of kyotorphin (KTP), a dipeptide (L-Tyr-L-Arg), on the level of sensory attention to stimuli of different modalities in rats and the exploratory behavior in goldfish were investigated. In both cases KTP was found to suppress the exploratory activity. When 5-HTP, a precursor of serotonin synthesis, is activated the inhibitory effects of KTP increased. It is assumed that the regulatory effect of KTP on the exploratory behavior of animals is mediated by the monoaminergic (neurotransmitting) brain systems, as distinct from its analgetic effects, which are mediated by the opioid brain systems.

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The stimulating effect of L-DOPA on exploratory activity of the ground squirrel in the hole-board and open field experiments was stronger in the spring than in autumn, whereas the regulating effect of the 5-HTP on adaptive behaviour of hibernating animals was stronger in autumn. Results of the biochemical analysis of the MAO A activity with serotonin or noradrenaline as substrates revealed a seasonal dependence of the substrate specific changes of this enzyme activity in hibernating animals. The data obtained suggest that the seasonal distinctions in effects of similar pharmacological agents depend on activity of the brain monoaminergic systems' activity in hibernating animals in different periods of the annual cycle.

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The effect of the ultralow power pulse-modulated electromagnetic radiation (EMR, power density 10 microW/cm2; carrying frequency 915 MHz; modulating pulses with frequency 2, 4, 6, 8, 12, 16 and 20 Hz) on activity of monoamine oxidase (MAO-A), enzyme involved in the oxidative deamination of monoamines, was investigated. It was established that the increase of activity MAO in hypothalamus reached the maximal meaning at modulation frequency of 6 Hz that corresponded 160% (p < 0.01) of the control level; and at modulation frequency of 20 Hz the decrease of enzyme activity up to 74% (p < 0.01) was found. Mainly the action of ultralow power pulse-modulated EMR on activity of MAO in hippocamp was activating; and the maximal increase of enzyme activity up to 174% (p < 0.01) was registered at modulation frequency of 4 Hz.

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