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Separation of hippocampal function in Morris water maze and in active place avoidance by alternance protocol
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hiadlovská, Zuzana (referee)
In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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Neuropharmacology of spatial navigation, cognitive coordination and flexibility tests in animal models
Prokopová, Iva ; Stuchlík, Aleš (advisor) ; Vyklický, Ladislav (referee) ; Blahoš, Jaroslav (referee)
Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...
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The effect of agonist of the metabotropic glutamate receptors LY 379268 in an animal model of psychosis
Rišňovská, Dominika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Introduction: Schizophrenia is a neuropsychiatric illness characterized by impairments in cognition and positive and negative symptoms. As currently used antipsychotics do not treat all symptoms of the disease, further research of the therapeutic potential of various drugs in the treatment of this disease is crucial. Psychosis is a condition or a mental state that usually accompany schizophrenia, as well as other disorders. We used MK-801, a non-competitive antagonist of NMDA receptors to induce an experimental model of psychosis in rats. By binding to the NMDA subtype of glutamate receptors located on inhibitory interneurons, MK-801 has been shown to elicit an overactivation of cortical and hippocampal pyramidal neurons, leading to behaviors such as hyperlocomotion, stereotypy or cognitive impairments. LY 379268, an agonist of group II metabotropic glutamate receptors, binds to both presynaptic and postsynaptic receptors on pyramidal neurons. It has been suggested that it could alleviate the MK-801-induced hyperactivity of the principal neurons. In this study, we sought to demonstrate the effects of LY 379268 in the MK-801 animal model of psychosis and hypothesized that LY 379268 will ameliorate deficits in the reversal learning induced by MK-801. Materials and methods: Long Evans rats received...
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Effects of NMDA receptor modulators on cell death in models of excitotoxicity in vitro.
Strnadová, Lenka ; Smejkalová, Tereza (advisor) ; Skřenková, Kristýna (referee)
NMDA receptors are ionotropic glutamate receptors (iGluR) activated by the amino acid glutamate and mediating signal transmission in the central nervous system. Their proper activity is essential for synaptogenesis, neuronal plasticity and synaptic transmission. However, excessive activation of NMDAR causes strong influx of calcium ions into neurons which triggers several destructive effects, eventually ending with cell death. This so-called excitotoxicity is present not only in many neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease, but also in acute pathophysiological conditions, such as stroke or traumatic brain injury. General NMDAR inhibitors that could potentially prevent neuronal excitotoxicity have shown severe negative side effects in models in vivo. On the other hand, selective inhibitors of NMDA receptors with the ability to block the unwanted excessive activity while preserving NMDAR physiological function have shown to be therapeutically useful. This work is going to briefly summarize the knowledge of structure, activation and localization of NMDA receptors, then it is going to describe their rule in mediating neuronal toxicity and a few methods we can use to study excitotoxicity in vitro. Finally, this work will compare the effects of several known NMDAR...
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Separation of hippocampal function in Morris water maze and in active place avoidance by alternance protocol
Vojtěchová, Iveta ; Petrásek, Tomáš (advisor) ; Hiadlovská, Zuzana (referee)
In this work, we examined the executive functions of the hippocampus at the behavioral level as a so-called behavioral separation in adult rats. We studied an impact of day-to-day alternation versus sequential learning (and the order of learning) of two spatial tasks (Morris Water Maze and Active Allothetic Place Avoidance) testing different hippocampal functions (experiment 1), or an impact of sequential versus alternating learning of one task (Active Allothetic Place Avoidance) in two different rooms (experiment 2), on performance. We found out that rats are able to learn both tasks as well as to discriminate between the two contexts regardless of the order or alternating of learning. Because such executive functions are impaired in human patients suffering from schizophrenia, we used this procedure also in the rat model of schizophrenia induced by acute intraperitoneal application of dizocilpine (MK-801), glutamate NMDA receptors antagonist, in the dose of 0.08 mg/kg. We failed to selectively disrupt the behavioral separation, however, we observed general learning deficit and hyperlocomotion regardless of the alternation in the Active Allothetic Place Avoidance task in these rats. The cognitive impairments in connection with learning after such low dose of MK-801 in this task have not yet been...
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Neuropharmacology of spatial navigation, cognitive coordination and flexibility tests in animal models
Prokopová, Iva ; Stuchlík, Aleš (advisor) ; Vyklický, Ladislav (referee) ; Blahoš, Jaroslav (referee)
Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...
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