Особенности процесса трещинообразования в массиве при управлении его газодинамикой

Исследован процесс сдерживания перехода угля из потенциально устойчивого состояния в стадию бурного разрушения. Ей, как правило, предшествует некоторый промежуток времени относительного затишья. Особенно важно улавливать этот момент среди массы различных откликов массива на ведение горных работ. Одним из вариантов управления развитием и релаксацией системы трещин может служить физико-химическая обработка.The inhibition process of coal transition from the potentially stable state in the stage of stormy destruction is investigation. As a rule, to it is preceded some interval of relative time calm. It is especially important to catch this moment among mass of different responses of array on the conduct of mountain works. Physical and chemical treatment can serve as one of control variants the development and relaxation of the cracks system

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala

Bacterial Lipopolysaccharide Increases Serotonin Metabolism in Both Medial Prefrontal Cortex and Nucleus Accumbens in Male Wild Type Rats, but Not in Serotonin Transporter Knockout Rats

It is well known that bacterial lipopolysaccharides (LPS) both increases proinflammatory cytokines and produces sickness behavior, including fatigue and anhedonia (i.e., the inability to experience pleasure). Previously, we have shown that intraperitoneally (i.p.) administered LPS increased extracellular monoamine metabolite levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), which was completely, or at least partly, prevented by pretreatment with a triple reuptake inhibitor that also blocks the serotonin (5-HT) transporter (SERT). This suggests indirectly, that LPS may enhance SERT transporter activity, and consequently, increase removal of 5-HT from the synaptic cleft, and increase metabolism of 5-HT. In the present study, we focus more specifically on the role of SERT in this increased metabolism by using rats, that differ in SERT expression. Therefore, the effects of an intraperitoneal LPS injection on extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were investigated by in vivo microdialysis in the NAc and mPFC of wild type (SERT+/+), heterozygous (SERT+/−) and knockout (SERT−/−) rats. Here, we show that LPS-induced 5-HIAA formation in male rats, is significantly increased in SERT+/+ rats in both the NAc and mPFC, whereas this increase is partly or totally abolished in SERT+/− and SERT−/− rats, respectively. Thus, the present study supports the hypothesis that systemic LPS in male rats increases SERT function and consequently enhances 5-HT uptake and metabolism in both the NAc and mPFC

Behavioral and Neuroendocrine Response to Psychosocial Stress in Male Rats:The Effects of the 5-HT 1A Agonist lpsapirone

The effect of the 5-HT 1A agonist ipsapirone on the behavior, plasma catecholamine, and corticosterone levels was studied in male Wistar rats during the psychosocial stress of confrontation with a confined dominant opponent 24 hr after defeat. The effect of the drug was also studied during a predefeat confrontation with the confined (would-be dominant) rat. Blood samples were withdrawn via a permanent heart catheter. The drug (5 mg/kg, ip) or vehicle was given 30 min before transportation to the experimental room. Ipsapirone had no major effects on the plasma hormone concentrations and had no influence upon the behavioral response to the confined rat. At the postdefeat test ipsapirone led to a significant increase of immobility, whereas both rearing and time spent sniffing the cage were diminished. Postdefeat psychosocial stress resulted in an increase of the hormone, particularly catecholamine levels. These responses were further elevated by the drug. The presence of high corticosterone levels in the home cage after postdefeat ipsapirone treatment leads to the hypothesis that postsynaptic 5-HT 1A receptor hypersensitivity develops after the social stress of defeat

Involvement of hypothalamic serotonin in activation of the sympathoadrenomedullary system and hypothalamo-pituitary-adrenocortical axis in male Wistar rats

Infusion of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (2.5-20 µg in 1 µl during 15 min), into the paraventricular nucleus of the hypothalamus (PVN) in the rat dose dependently increased plasma adrenaline and corticosterone concentrations, without affecting plasma noradrenaline concentrations. The highest dose also increased plasma glucose levels significantly. The results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis are activated after stimulation of 5-HT1A receptors in the PVN.

Urine ethanol concentration and alcohol hangover severity

Background: The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. Methods: N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. Results: Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. Conclusion: Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms

Behavioural Physiology of Serotonergic and Steroid-Like Anxiolytics as Antistress Drugs

Pharmacological studies are useful tools to understand the neurobiological basis of behavioural and physiological stress mechanisms. Ipsapirone, a 5-HT1A autoreceptor agonist is a representative of novel anxiolytics without the disadvantages of benzodiazepam-like drugs. Behavioural, physiological and neuroendocrine studies in the rat are reviewed which were aimed to investigate the antistress properties of ipsapirone during reexposure to various conditioned emotional stress situations. It is demonstrated that in certain situations, probably due to a stress-induced sensitisation of postsynaptic 5-HT1A receptors, anxiolytic doses of the drug may show prostress (anxiogenic) behavioural and neuroendocrine effects. Furthermore, brain corticosteroid receptors, probably interacting with the serotonergic transmission, are involved in anxiogenic/prostress processes. In this respect antagonists of the brain mineralocorticoid-like (type I) receptors may be important antistress drugs of the future.

The many different faces of major depression: it is time for personalized medicine

First line antidepressants are the so-called SSRIs (selective serotonin reuptake inhibitors), e.g. fluvoxamine, fluoxetine, sertraline, paroxetine and escitalopram. Unfortunately, these drugs mostly do not provide full symptom relief and have a slow onset of action. Therefore other antidepressants are also being prescribed that inhibit the reuptake of norepinephrine (e.g. reboxetine, desipramine) or the reuptake of both serotonin (5-HT) and norepinephrine (e.g. venlafaxine, duloxetine, milnacipran). Nevertheless, many patients encounter residual symptoms such as impaired pleasure, impaired motivation, and lack of energy. It is hypothesized that an impaired brain reward system may underlie these residual symptoms. In agreement, there is some evidence that reuptake inhibitors of both norepinephrine and dopamine (e.g. methylphenidate, bupropion, nomifensine) affect these residual symptoms. In the pipeline are new drugs that block all three monoamine transporters for the reuptake of 5-HT, norepinephrine and dopamine, the so-called triple reuptake inhibitors (TRI). The working mechanisms of the above-mentioned antidepressants are discussed, and it is speculated whether depressed patients with different symptoms, sometimes even opposite ones due to atypical or melancholic features, can be matched with the different drug treatments available. In other words, is personalized medicine for major depression an option in the near future

The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases monoamine release in the prefrontal cortex of olfactory bulbectomized rats

The first line of antidepressant treatment nowadays are selective serotonin reuptake inhibitors. Although they are relatively safe to use, selective serotonin reuptake inhibitors (SSRIs) can induce severe side effects. New promising antidepressants may be the triple monoamine reuptake inhibitors, which not only enhance serotonin and norepinephrine neurotransmission, but also increase brain dopamine levels. Recently it has been shown that one of the triple reuptake inhibitors, DOV 216,303 has antidepressant-like effects in the olfactory bulbectomy (OBX) model of depression, but the alterations in monoaminergic neurotransmission in these animals are still unknown. In the present study we investigated not only the effect of acute, but also chronic treatment of DOV 216,303 in OBX rats on monoamine and metabolite levels. The main results are decreased baseline dopamine levels in the prefrontal cortex one day after OBX, while 38 days after OBX no difference could be observed in monoamine levels after vehicle treatment. Treatment with DOV 216,303 leads to increased extracellular levels of serotonin and norepinephrine neurotransmission, but also increased dopamine levels in OBX animals as well as their controls. This increase could be observed after one single administration, but also after chronic treatment. However, a DOV 216,303 challenge in chronically treated animals resulted in lower monoamine concentrations than the same challenge in untreated animals. More research is needed to investigate this seemingly hyporesponsivity to chronic DOV 216,303 treatment. (C) 2010 Elsevier B.V. All rights reserve