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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Epigenetic mechanisms in psychostimulant addiction
Kubátová, Eliška ; Novotný, Jiří (advisor) ; Rydzyková, Tereza (referee)
Psychostimulants are highly addictive substances that act in a brain reward center by increasing extracellular levels of monoamines. In western civilization, they have gained popularity during the 20th century. Psychostimulant addiction is a persistent social problem even today since therapy is often unsuccessful and former users relapse frequently. Alterations in gene expression occur after psychostimulant is administered. These changes are long-lasting as they can often persist for weeks and months. This work focuses on the epigenetic changes in a brain associated with the development of addiction after psychostimulant administration. Key words: Epigenetics, psychostimulants, amphetamine, methamphetamine, cocaine, addiction
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Molecular mechanisms of sleep homeostasis
Dvořáková, Tereza ; Spišská, Veronika (advisor) ; Rydzyková, Tereza (referee)
Sleep is an essential physiological process driven by a circadian system with its main endogenous pacemaker in the suprachiasmatic nucleus of hypothalamus (SCN) and by sleep homeostasis, a process reflecting time spent awake. This work is focused on basic characteristics of sleep, describes the two process model of sleep regulation and sleep homeostasis theory which connects synaptic plasticity with sleep. Next it describes the function and principles of the circadian system including the synthesis of melatonin and the principles of homeostatic sleep regulation. Within the sleep homeostasis, the focus is on the role of dopamine, prostaglandin D2 and especially adenosine. Next are discussed genes involved in sleep homeostasis and connecting it with synaptic plasticity. Last are mentioned alterations in homeostatic regulation of sleep in people suffering from depression and the final chapter focuses on the interactions between circadian and homeostatic process, particularly on the role of clock genes in sleep homeostasis. Key words: sleep, circadian system, sleep homeostasis, adenosine
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The effect of morphine on neurogenesis and neurodegeneration in rat brain
Rydzyková, Tereza ; Novotný, Jiří (advisor) ; Vodička, Martin (referee)
Morfin is a clinically used analgesic drug but also an abusive drug. It has an impact on a wide range of CNS regions (nucleus accumbens, ventral tegmentum, hippocampus, etc.) and affects their functions, e.g. cognitive functions or anxiety. Although the results of so far published studies are often contradictory, the effects on cell death and proliferation in the CNS have been demonstrated. In this work, we focused on how chronic administration of morphine and subsequent withdrawal of this drug affects neurogenesis and neurodegeneration in the rat brain and how it affects some markers involved in the addiction and post-drug-induced condition. We have succeeded in introducing immunohistochemical markers for monitoring neurogenesis (bromodeoxyuridine and doublecortin) and neurodegeneration (Fluoro-Jade C) and for detection of selected neuromodulatory peptides (cholecystokinin and neuropeptide Y). We have found that morphine may influence the process of neurogenesis and neurodegeneration, but its effects differ in different CNS structures (nucleus accumbens, hippocampus, and amygdala). Key words: Morphine, brain, rat, withdrawal syndrom, neurogenesis, neurodegeneration
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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