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The effect of morphine withdrawal on G protein-coupled receptors and redox balance in rat brain
Kočárková, Veronika ; Novotný, Jiří (advisor) ; Černá, Barbora (referee)
Although morphine is one of the most effective analgesics available, its long-term use is severely limited by the development of tolerance and dependence. Molecular mechanisms responsible for these effects have been the focus of intensive research for decades aimed at developing safer and more effective pain treatments. The aim of this thesis was to contribute to a better understanding of the molecular actions of morphine, as an understanding of these processes is essential to develop better therapeutic approaches. Using western blot analysis, we investigated the effect of 10-day treatment with increasing doses of morphine and its subsequent withdrawal on key components of opioid signalling in the rat cerebellum and cerebral cortex. Amounts of opioid receptors, various heterotrimeric G protein subunits, GRK3 kinase and β-arrestin 2 were examined. Furthermore, the levels of adenosine A3 receptor and cannabinoid receptor type 1 were detected. Finally, we also investigated the effect of morphine and its withdrawal on oxidative stress markers. Morphine administration resulted in a significant decrease in GRK3 kinase levels in both brain regions, and these changes remained even after withdrawal. However, there was no significant change observed in the content of opioid receptors, different G protein...
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