Properties of glutamate receptor subunit GluN2B antagonists and effects of prenatal opioid exposure: Studies in chicken and rat
Appears in the following Collection
- Farmasøytisk institutt 
AbstractThe NMDA-receptor is a central part of the machinery that enables us to learn, form memories and develop a normal brain. It is expressed all over the central nervous system and is responsible for signalling between nerve cells. Abnormal changes in the expression and location of the NMDARs are associated with neurological disease. Consequently, these receptors are interesting targets for probes and drugs. However, due to their complicated pharmacology, such molecules are scarce and in high demand. An important ambition in research is to reduce, replace and refine experiments that involve animal models. The use of chicken embryos adheres to these principles. We have therefore validated the chicken embryo as a model for NMDAR research by combining laboratory testing of new antagonists with computer modelling of the antagonist-receptor complexes. This has provided knowledge about the receptor function and the chemical requirements for potent antagonists. After validating the chicken model, we exposed both chicken and rat embryos to opioids during gestation, and found that the exposure affected both NMDAR function and composition. Research on the potential effects of maternal drug use on children is important, considering the worldwide increase of opioid abuse.
List of papers
|Paper I: Exploring the overlapping binding sites of ifenprodil and EVT-101 in GluN2B containing NMDA receptors using novel chicken embryo forebrain cultures and molecular modelling. Marthe Fredheim Fjelldal, Thibaud Freyd, Linn. M. Evenseth, Ingebrigt Sylte, Avi Ring, Ragnhild E. Paulsen. Pharmacology Research and Perspectives (2019), DOI: 10.1002/prp2.480. The article is included in the thesis. Also available at: https://doi.org/10.1002/prp2.480|
|Paper II: Functional analysis of the EVT-101 binding site using new GluN2B non-competitive antagonists. Marthe Fredheim Fjelldal, Jimmy E. Jakobsson, Ragnhild Paulsen. Unpublished manuscript. To be published. The paper is not available in DUO awaiting publishing.|
|Paper III: Opioid receptor-mediated changes in the NMDA receptor in developing rat and chicken. Marthe Fredheim Fjelldal, Mussie Ghezu Hadera, Mette Kongstorp, Lars Peter Engeset Austdal, Ana Šulović, Jannike Mørch Andersen, Ragnhild Elisabeth Paulsen. International Journal of Developmental Neuroscience (2019), DOI: 10.1016/j.ijdevneu.2019.07.009. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.ijdevneu.2019.07.009|