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Role of glutamatergic transmission in mechanisms of addiction to morphine.
Moutelíková, Karolína
;
Hejnová, Lucie
(advisor) ;
Červená, Kateřina
(referee)
Drugs are used by mankind since ancient times. One group of these substances are opioids. Opioids have antinociceptive effects and can induce euphoria and relaxation as well. A chronic usage of opioids can lead to a development of drug addiction and phenomens like tolerance and sensitization. One of the most used opioids in medicine is morphine. Morphine is isolated from opium of poppy (Papaver somniferum). Direct effect of morphine is mediated via activation of μ- opioid receptors and their signal cascade. It was implicated that the usage of morphine affects other neurotransmmiter systems in the brain and these neurotransmmiter systems play a signifikant role in the development of addiction and other phenomena. One of these systems is an important excitatory brain system - glutamergic system. This bacherol thesis focuses on interrelationship between opioid and glutamatergic systems during addiction.There were described changes in a composition of glutame ionotropic receptors and changes in their expression as well as in expression of metabotropic glutamate receptors. These changes differ in various parts of the brain and in diverse stages of addiction on morphine too. In spite of all diferences, the results of studies indicate that glutamatergic receptors play a significant role in the development...
Detailed record
Role of glutamatergic transmission in mechanisms of addiction to morphine.
Moutelíková, Karolína
;
Hejnová, Lucie
(advisor) ;
Červená, Kateřina
(referee)
Drugs are used by mankind since ancient times. One group of these substances are opioids. Opioids have antinociceptive effects and can induce euphoria and relaxation as well. A chronic usage of opioids can lead to a development of drug addiction and phenomens like tolerance and sensitization. One of the most used opioids in medicine is morphine. Morphine is isolated from opium of poppy (Papaver somniferum). Direct effect of morphine is mediated via activation of μ- opioid receptors and their signal cascade. It was implicated that the usage of morphine affects other neurotransmmiter systems in the brain and these neurotransmmiter systems play a signifikant role in the development of addiction and other phenomena. One of these systems is an important excitatory brain system - glutamergic system. This bacherol thesis focuses on interrelationship between opioid and glutamatergic systems during addiction.There were described changes in a composition of glutame ionotropic receptors and changes in their expression as well as in expression of metabotropic glutamate receptors. These changes differ in various parts of the brain and in diverse stages of addiction on morphine too. In spite of all diferences, the results of studies indicate that glutamatergic receptors play a significant role in the development...
Detailed record
Role of metabotropic glutamate receptors and their associated proteins in physiology and pathophysiology
Kumpošt, Jiří
;
Blahoš, Jaroslav
(advisor) ;
Dráber, Petr
(referee) ;
Viklický, Vladimír
(referee)
of the thesis Glutamate is a main excitatory neurotransmitter in the brain of mammals, which activates both ionotropic and metabotropic glutamate receptors. Ionotropic receptors are responsible for fast synaptic transmission leading to membrane depolarization and Ca2+ influx into the cell. On the other hand mGlu receptors play an important role in regulation of the transmission via heterotrimeric G-proteins and activation of various signaling pathways. Postsynaptically localized group I mGlu receptors (mGluR1, 5) together with ionotropic NMDA and AMPA receptors share common large receptor signaling complexes, or signalosome facilitating glutamate signal transductions. Individual mGluR1 splice variants are differently associated with signalosome including scaffold proteins like PSD-95 which organize postsynaptic density (PSD). Heterodimerization of different mGluR1 splice variants is a focal point of my thesis together with investigation of recently discovered protein IL1RAPL1 (interleukin-1 receptor accessory protein-like 1) and its role in organization of postsynaptic signalosome. Using biochemical, immunocytochemical and functional assays we showed heterodimers of mGluR1a/1b were expressed on the plasma membrane and that heterodimers are fully functional in the recombinant system. Next we showed...
Detailed record
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