AN ANALYSIS OF NMDA AND BETA-ADRENERGIC RECEPTOR ANTAGONISTS ADMINISTRATION AND NEURAL C-FOS EXPRESSION FOLLOWING CONDITIONED CONTEXT AVERSION LEARNING IN MICE

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2023-3-17

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İlhan, Furkan

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Cancer patients develop anticipatory nausea and vomiting (ANV) following chemotherapy treatment as a result of classical conditioning learning. Although researchers have been conducting clinical studies to understand the characteristics of ANV, animal models can also be utilized to develop novel diagnostics and therapeutics. Conditioned context aversion (CCA) has been accepted to arise from classical conditioning and used as an animal model of ANV. Although antiemetic agents were widely used to prevent nausea and vomiting, 25% of cancer patients still develop ANV. However, the formation of memories can be prevented during consolidation phase of memory formation. We conducted two experiments (Experiment 1 and Experiment 2) to investigate memory impairing effect of N-methyl-D-aspartate antagonist MK-801 and beta-adrenergic antagonist propranolol on CCA. We found that systemic administration of propranolol but not MK-801 prevented animals from developing CCA. v Although behavioral research mainly established the principles of CCA learning, it’s neural substrate is yet to be investigated. Experiment 3 was conducted to identify the brain regions involved in CCA learning. We found elevated c-Fos expression in the prelimbic division of the medial prefrontal cortex, IC, basolateral nucleus of the amygdala, CA1-CA2 and dentate gyrus subregions of the hippocampus, indicating that these brain regions are activated following CCA. To the best of our knowledge, ours is the first study finding memory impairments induced by beta-adrenergic receptor antagonist in CCA and showing neural correlates of CCA learning. Further research is necessary to unravel causal involvement of these brain regions in the development of CCA.

Subject Keywords

anticipatory nausea and nausea, cancer, conditioning, learning, mice

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https://hdl.handle.net/11511/102573

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Graduate School of Social Sciences, Thesis

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Citation Formats

F. İlhan, “AN ANALYSIS OF NMDA AND BETA-ADRENERGIC RECEPTOR ANTAGONISTS ADMINISTRATION AND NEURAL C-FOS EXPRESSION FOLLOWING CONDITIONED CONTEXT AVERSION LEARNING IN MICE,” M.S. - Master of Science, Middle East Technical University, 2023.