Role of the Dynorphin/KOR System in Mediating the Stress Response in Mice

Alcohol and drug abuse represent two of today’s greatest unsolved public health problems. The dynorphin/kappa opioid receptor (KOR) system has been shown to mediate the increased rewarding effects of drugs of abuse and the increased anxiety and stress seen during alcohol withdrawal. In the present study, we examined the role of the dynorphin/KOR system in the Bed Nucleus of the Stria Terminalis (BNST) in stress related behaviors using an animal model. We stereotaxically injected mice with an inducible caspase construct to selectively destroy dynorphin cells in the BNST and tested mice using the elevated plus maze (EPM), open field, and forced swim stress (FSS) behavioral paradigms. Our results show that under basal, non-stress conditions, ablating dynorphin from the BNST does not produce significant changes in behavior. However, dynorphin and KORs may play an important role in mediating behavior following a stressful event (FSS). Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that functionally inhibiting dynorphin neurons in the BNST may have an anxiogenic effect under stressful conditions faced in the FSS-EPM behavioral paradigm. These results, along with an ongoing set of behavioral experiments with the DREADD mice, may provide novel insight for the role of the dynorphin/KOR system in mediating the stress response relevant to alcohol and drug use disorders.Bachelor of Scienc