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Assessment of the impact of phenytoin on motor activity development of laboratory rats by motor activity testing and swimming analysis
Matoušková, Kateřina ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Phenytoin is well-known antiepileptic drug with high anticonvulsant effect but also with proven side effects on motor activities associated with its long-term use. This thesis summarizes side effects of phenytoin on motor skills and coordination of rats after acute phenytoin treatment. Theoretical part includes proven effects of phenytoin on human and animal model. Knowledge about motor skills development of rats and comparison with human motor skills development is also included in the thesis. Apart from locomotion development, swimming development is also described. We compared three groups of rats in the experiment. Each group consisted of ten rats. We compared group with dosage 60 mg/kg, 30 mg/kg, control group and vehicle group. Each group was tested before application for control. We tested animals on postnatal day 12, 18 and 25. Effects of phenytoin were evaluated by motor skills testing and swimming analyses. The results of this thesis have proved impaired motor skills and coordination after phenytoin treatment of 12 and 25 days old rats.
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Animal model of schizophrenia and time-space integration in the role of AAPA
Janďourková, Pavla ; Nekovářová, Tereza (advisor) ; Valeš, Karel (referee)
Temporal and spatial cognition constitute basic elements of the cognitive function. Both of these competences are important for the individual's orientation and survival and there are likely to be different interactions between them. Perception of time, unlike spatial navigation and memory, is less explored. Impairments of interval timing occur in many neurodegenera- tive and neuropsychiatric disorders. According to current studies it is evident that timing is impaired even in patients with schizophrenia, but the results are still ambiguous. The aim of our work was to test the AAPA task in the time-place integration in the ani- mal model of schizophrenia. In the future, it could help to clarify the impairments of the time perception in patients with schizophrenia. In contrast to the classic AAPA task, our version included alternating of phases of light and darkness. The assumption of the experiment was that the solution of the task by rats in the dark is more dependent on the timing strategy than the solution of the task during the light, which is dependent on the spatial orientation. In the first phase of the experiment, the rats adopted both strategies - spatial (during the light phase of the session) and timing (during the dark phase). In the next phase of the experiment, we tested the animal...
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Experimental models of ischemic brain injury
Alexová, Daniela ; Valeš, Karel (advisor) ; Alterová, Kateřina (referee)
Title: Experimental models of ischemic brain injury Author: Daniela Alexová Department: Department of Physiology Supervisor: RNDr. Karel Valeš, Ph.D. Abstract: This bachelor thesis focuses on the experimental models of ischemic brain injury closely related to one of the most common forms of brain damage, the ischemic stroke. This type of brain injury is connected to subsequent serious neurological deficits. The studies of experimental models of ischemic brain injury are therefore essential for primary and secondary research. The first two parts of the thesis are dedicated to brief characterization of stroke with focus on types of stroke, incidence, risk factors and molecular mechanism of injury. Next part summarizes the challenges of experimental modeling of ischemic brain injury and the specifics of small and big laboratory animals. The core of the thesis is the description of 11 most frequently used models. Selected models were divided into focal and global models and in each of these categories were furthermore characterized according to procedural performance, animal mortality or success of lesion induction. The key modifications of models introduced during the years in order to increase the reproducibility of brain injury are described as well. All 11 selected experimental models are summarized at the...
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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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