When an organism is exposed to a wide range of stressors, a neuroendocrine cascade leads to the release of stress hormones (corticosteroids) into the bloodstream. The corticosteroids produce changes in physiology and brain function that are crucial for dealing with emergencies, but persistent elevation of corticosteroids produce the well known deleterious effects of stress. All vertebrates need a rapid and robust stress response as well as an effective means of terminating this response. The brain mechanisms that terminate this response remain poorly understood. These studies investigate a novel mechanism through which stress hormones could provide negative feedback to terminate the stress response. Collaborative experiments will be conducted at Arizona State University, University of Colorado and University of South Dakota to test the hypothesis that corticosteroids block clearance of the neurotransmitter serotonin in specific brain regions during a stress response leading to negative feedback and associated changes in behavior. State-of-the-art neurochemical, brain imaging and behavioral studies will determine whether corticosteroids block serotonin transport via a newly described transporter in brain, leading to enhanced serotonin signaling and suppression of the stress response. These studies will also serve to train students (graduate, undergraduate, and high school) and post-doctoral researchers in cutting-edge neuroscience research. The research training provided by the principle investigators (PIs) is important for encouraging young students to appreciate scientific reasoning and pursue careers in science. Collectively, the PIs have sponsored over 100 undergraduate research projects from students with diverse backgrounds, and each of the PIs also has a long track record of dedication to graduate student education and research. With these studies, each PI will continue to make explicit efforts to reach out to economically disadvantaged or underrepresented groups.
