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Does prenatal methamphetamine exposure induce cross-sensitisation to drugs in adult male and female rats?
Macúchová, Eva ; Šlamberová, Romana (advisor) ; Šulcová, Alexandra (referee) ; Valeš, Karel (referee)
Women, who abuse drugs during pregnancy, expose not just themselves but also their developing foetus to impairing effects, which can have potentially harmful and even long- term effects on the exposed children. For some years, methamphetamine (MA) has dominated the illicit drug market in the Czech Republic and Slovakia; additionally this drug is on the rise worldwide. It is one of the most accessible drugs, and in many cases the first choice drug for many drug-addicted pregnant women; in part due to its anorectic and stimulant effects. These women are rarely aware of the consequences of their behaviour and their pregnancy is hardly ever a good enough reason for giving up drug use. These findings are supported by many experimental studies that show the damaging effects of maternal MA exposure on their offspring. There is growing evidence that exposure to MA in utero not only causes birth defects and delays in infant development, but also impairs the brain reward neural pathways of a developing offspring in such a way, that it could increase the predisposition for drug addiction later in life. Previously published animal studies have shown that offspring of mothers exposed to MA during pregnancy are more sensitive to MA when they encounter this drug later in adulthood. With respect to increased...
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Neurobiology of hypoxic-ischemic insult in immature brain
Kuchtiak, Viktor ; Valeš, Karel (advisor) ; Hejnová, Lucie (referee)
Pathology of the hypoxic-ischemic insult is very well described in the adult age, whereas the state of knowledge is largely neglected during the perinatal age. Serious insult in the early postnatal age leads often to the permanent neurological consequences or death. Ischemic insult causes over release of the glutamate in a brain tissue. This process is followed by excitotoxic damage of the tissue. Glutamatergic NMDA receptors play a key role in the excitotoxicity. Over-activated NMDA receptors are one of the possible therapeutic approaches against ischemic damage of the brain. Speaking of contemporary projects focusing on perinatal stroke, it is necessary to take into account developmental differences in the brain tissue and the requirements to minimal toxicity of possible drugs. Pharmacotherapies for hypoxic-ischemic damage implemented in the current perinatology are insufficients.
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Neurobiology of hypoxic-ischemic insult in immature brain
Kuchtiak, Viktor ; Valeš, Karel (advisor) ; Hahnová, Klára (referee)
Pathology of the hypoxic-ischemic insult is very well described in the adult age, whereas the state of knowledge is largely neglected during the perinatal age. Serious insult in the early postnatal age leads often to the permanent neurological consequences or death. Ischemic insult causes over release of the glutamate in a brain tissue. This process is followed by excitotoxic damage of the tissue. Glutamatergic NMDA receptors play a key role in the excitotoxicity. Over-activated NMDA receptors are one of the possible therapeutic approaches against ischemic damage of the brain. Speaking of contemporary projects focusing on perinatal stroke, it is necessary to take into account developmental differences in the brain tissue and the requirements to minimal toxicity of possible drugs. Pharmacotherapies for hypoxic-ischemic damage implemented in the current perinatology are insufficients.
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Influencing motor activity in laboratory rat offspring by specific antagonist of AMPA receptors.
Soukupová, Andrea ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
The IEM 1460 is a potential age-specific anticonvulsant and an indicator of the distribution of AMPA receptor subtypes among rat brain cells. It is a derivative of adamantane, that was tested in previous studies on models of human myoclonic and generalized tonic-clonic seizures with promising results. In this thesis we evaluated its effect on the motor activity of rat offspring in the age of 12, 18 and 25 days, we used 90 animals in total . The effect was evaluated 30 minutes after intraperitoneal administration of IEM 1460 in two doses, 10 mg/kg or 20 mg/kg, and was compared to the control animals with physiological solution applied intraperitoneally in amount of 20 mg/kg. To test the animals we used Open field test, righting reflex, negative geotaxis, horizontal bar test, rope climbing test, regular and irregular horizontal ladder test. The tests were applied to animals in mentioned order. There were found significant changes influencing motor behaviour, primarily in the 12 days old animals with the dose of 20 mg/kg IEM 1460 and in the 25 days old animals with both doses of IEM 1460, 10 and 20 mg/kg. In the 18 days old animals the results were less significant. Powered by TCPDF (www.tcpdf.org)
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Possible influencing the motor performance of developing rats by repeated administration of the NMDA receptor antagonist specific for NR2 subunit
Kozlová, Lucie ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Nonspecific NMDA receptor antagonists induce hyperlocomotion in rats. The aim of this work is to determine whether the NMDA receptor antagonist specific for NR2 subunit exhibit similar negative effect as nonspecific antagonists. This subunit is predominant in the brain in the early postnatal period. The introduction summarizes the data on NMDA receptors and the development of rat. The experimental part deals with the action of a specific NMDA receptor antagonist Ro 25-6981 on motor performance of developing rats. Substance was repeatedly administered to rats at postnatal days 7 to 11. Spontaneous locomotion and motor performance of the animals were repeatedly tested up to adulthood by battery of tests appropriate for individual ages. Our research demonstrated that this substance does not have significant effect on motor system of laboratory rat and that it might be further tested as a possible age-bound antiepileptic drug.
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Automated monitoring of behaviour as a new paradigm in the research of depressive disorder
Revayová, Anna ; Valeš, Karel (advisor) ; Kubik-Zahorodna, Agnieszka (referee)
The rapid antidepressant effect of ketamine changed the direction of the research of potential antidepressants and its effect was also evaluated in this thesis. However, the main focus of this thesis is a new methodological approach to the research of depressive disorder. The main interest lies with the evaluation of automated monitoring of behaviour in this research. The first aim of this thesis was to evaluate the antidepressant effect of ketamine in the forced swimming test using software enabling automated monitoring of behaviour. The second aim was to meassure the change in phosphorylated Mammalian target of rapamycin (mTOR), using Enzyme-Linked ImmunoSorbent Assay (ELISA). The last, but the most important aim of this thesis was to implement the utilization of Phenotyper boxes in the automated behavioural evaluation of the olfactory bulbectomy model of depressive disorder and also evaluate the effect of ketamine in this model. Ketamine did not show an antidepressant effect in forced swimming test, however this observation could be influenced by chosen dose and mouse strain. Sensitivity of the test to chosen experimental protocol shows insufficient validity of this test. Observed change in level of phosphorylated mTOR corresponded with the behavioural results. Data collected from Phenotyper...
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Biological significance of neuroactive steroids in animal models of brain diseases
Rambousek, Lukáš ; Valeš, Karel (advisor) ; Votava, Martin (referee) ; Chvátal, Alexandr (referee)
Neurosteroids play an important role in the brain physiology and pathophysiology. They control inhibitory and excitatory neurotransmission. The presented thesis aims to investigate the biological significance of neuroactive steroid 3_5_-pregnanolone glutamate (3_5_P-Glu). We investigate the effect of 3_5_P-Glu in naïve rats. Next, we evaluate the effects of 3_5_P-Glu in animal model of schizophrenia and excitotoxic lesion of hippocampus induced by N-methyl- D-aspartate (NMDA). Furthermore, we morphologically characterize the NMDA lesion model. 3_5_P-Glu did not induce significant psychotomimetic side effects such as hyperlocomotion, sensorimotor grating deficit or memory impairment. Next, 3_5_P-Glu showed dose dependent pro-cognitive effects in animal model of schizophrenia; however, it had no effect on hyperlocomotion in this model. 3_5_P-Glu also ameliorated spatial learning deficit of rats induces by NMDA lesion of hippocampi in the Carousel maze and had mild effect on NMDA induced damage of hippocampus when applied before. Additionally, the morphological analysis of hippocampal NMDA lesion revealed overexpression of NMDA receptor NR1 and NR2B and downregulation of GABAA receptor _5 subunits. The lesion was very conservative, did not spread to other structures and did not affect GABAergic...
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Antidepressant effect of ketamine
Revayová, Anna ; Valeš, Karel (advisor) ; Šóš, Peter (referee)
Ketamine is used as an anaesthetic mainly in veterinary medicine and paediatrics. Thirteen years ago, interest in ketamine as an antidepressant emerged. Ketamine as an antidepressant works rapidly and is also effective in the case of patients suffering from treatment resistant depression.The main disadvantage of ketamine as an antidepressant is its psychotomimetic effect. Ketamine is an antagonist of the NMDA receptor, which has an important influence in brain activity. Through antagonism of this receptor, a large amount of processes can be affected, for example levels of glutamate, excitotoxicity, or density of other receptors. In addition, ketamine probably also affects the D2 receptors, but its role in this is uncertain. Ketamine influences synaptic plasticity and its effect can be modulated by repeated application, co-application with other drugs and other methods. Also gender seems to play role in the effect of ketamine. The aim of this work is to summarise possible mechanisms of effect of ketamine, its effect on synaptic plasticity and also possibilities of modulation of its effect. This thesis mentions the most important studies concerning ketamine as an antidepressant and possible future directions of research. Keywords: major depressive disorder, ketamine, antidepressant, NMDA antagonism,...
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