Morphine is used to treat moderate to severe acute and chronic pain, but it is also frequently abused. This carries a high risk of developing tolerance and dependence, which can lead to long-lasting changes in the central nervous system. To date, there is only limited knowledge about the consequences of morphine administration during the period of gestation and weaning on the brain of the offspring. This project will investigate the presumed changes at the molecular level of selected parts of the brain of rats exposed to morphine during prenatal and early postnatal life. We will examine the involvement of epigenetic modifications in the regulation of gene expression, with a particular focus on the expression of selected transcription factors, observe changes in neurotransmission signaling and perform proteomic profiling of the cortex, hippocampus, striatum and cerebellum of young and adults rats. In parallel, the rats will undergo behavioral testing to uncover possible changes in their behavior related to previous perinatal morphine exposure. These studies may contribute to a better understanding of the complex consequences of uncontrolled maternal opioid use during pregnancy and reveal new molecular targets useful for the development of innovative approaches to the treatment of drug dependence.
Five relevant publications of the research group:
Drastichova Z., Hejnova L., Moravcova R. and Novotny J. (2021) Proteomic analysis unveils expressional changes in cytoskeleton- and synaptic plasticity-associated proteins in rat brain six months after withdrawal from morphine. Life 11:683.
Pacesova D., Spisska V., Novotny J. and Bendova Z. (2021) Maternal morphine intake during pregnancy and lactation affects the circadian clock of the rat pups. Brain Res. Bull. 177:143-154.
Ujcikova H., Eckhardt A., Hejnova L., Novotny J. and Svoboda P. (2022) Alterations in the proteome and phosphoproteome profiles of rat hippocampus after six months of morphine withdrawal; comparison with the forebrain cortex. Biomedicines 10:80.
Mali A.S., Honc O., Hejnova L. and Novotny J. (2023) Opioids ameliorate oxidative stress via the Nrf2/HO-1 signaling cascade in LPS-stimulated microglia. Int. J. Mol. Sci. 24:11089.
Pacesova S., Spisska V., Novotny J. and Bendova Z. (2023) Methadone administered to rat dams during pregnancy and lactation affects the circadian clock of their pups. J. Neurosci. Res. 101:1737-1756.Apply to the project