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CRF receptor-mediated sensitization of 5-HT2A receptor signalling

Principal Investigator:
  • Cornelia Walther, University of Western Ontario

Project Overview

Anxiety and depression often present as co-morbid disorders and the expression and severity of these illnesses is commonly associated with stressful experiences. Both are widespread and serious disorders that affect the lives of 10-15% of Canadians for most of their lifetime. There are multiple potential causes of depression, including genetic predisposition, but the majority of cases are influenced by environmental and social factors. The variability of symptoms and responses to therapeutic treatment emphasizes the incredible complexity of the underlying neurobiology of these diseases. There is an urgent need to develop new efficacious drugs that treat stress/anxiety and depression without negative side effects of current drug treatments. Recently, the cellular basis for how stress promotes anxiety and depression has been discovered. Specifically, an interaction between two receptor proteins in the brain (members of the G protein-coupled receptor (GPCR) family, the CRFR1 and serotonin receptor 2A (5-HT2AR), has been identified. 5-HT2 family receptors in the brain represent major molecular targets for drugs used in the treatment of depression and anxiety. This project is designed to better understand fundamental molecular mechanisms that link stress to anxiety. It will provide a detailed analysis of the molecular mechanisms underlying the regulation of 5-HT2AR signalling by CRFR1 and how the activated receptors can change the biology of the brain in anxiety and depression.