The aim of this study is to lay the foundation for the development of a novel paradigm to study the effects of corticotropin-releasing hormone (CRH) released from the bed nucleus of the stria terminalis (BNST) on fear and anxiety responses in rodents. The BNST is a stress-responsive, sexually dimorphic brain region and repeated, low-level activation of its CRH receptors is known to cause a chronic heightened stress response. We are interested in utilizing a chemogenetic technique known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in order to selectively manipulate these CRH-containing neurons. However, previous generations of the ligands typically used in this technique have been shown to have significant drawbacks, including low affinity and “off-target” effects that can impact the results of the manipulations. A novel ligand, JHU37160, has recently been developed with a demonstrated high affinity for the designer receptors and substantial ability to penetrate the blood-brain barrier (BBB). We are using this study to establish that this ligand will not produce “off-target” effects. To do this, we are administering the ligand via intraperitoneal (IP) injection to adult rats that do not express DREADDs and comparing their behavior in an open-field test to a control (vehicle) group. We are expecting to see no significant differences between the groups across all behavioral measures. If so, we can move forward with the development of the paradigm to use DREADDs to further investigate how CRH-containing neurons in the BNST impact fear and anxiety responses in rodents. It is also adding to the current body of knowledge on DREADDs and specific designer drugs, as JHU37160 is still a novel ligand. This experience has allowed me to enrich my knowledge in the field of neuroscience and working in this lab has taught me a multitude of valuable life and career skills.
Author(s): Madelynne Hall, Psychology and Neuroscience
Major Advisor(s): Jennifer Quinn, Department of Psychology
Jacob Dowell, Department of Psychology
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