THE INTERACTIVE AND INDIVIDUAL EFFECTS OF OREXIN A AND NEUROTENSIN IN THE BRAIN ON SPONTANEOUS PHYSICAL ACTIVITY A Thesis SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY

i Acknowledgements I would like to express sincere gratefulness to: My advisor, Dr. Catherine Kotz, who has supported and encouraged me throughout these years to complete this project. She has taught me a type of work-ethic that I never had before. Martha Grace who has helped me with many experimental procedures. I could not have done anything without her help. Dr. Charles Billington for his support in my experimental designs, interpretations, thesis writing, and presentation. Dr. Blake Gosnell for his support in thesis writing and for serving on my committee. Dr. James Cleary for serving on my committee. Dr. Jen Teske who has helped me to understand the principles and techniques of our lab and encouraged me with her ―down-to-earth lab wisdom‖. Dr. Joshua Nixon who has helped me with immunohistochemistry and made difficult things seem easy. Dr. Tammy Butterick who advised me on antibodies and also gave me advice about scientific working, thinking, and living. (PhD Candidate) who has taught me immunohistochemistry and set an example of science work-ethic in our lab. Mark Margosian who has helped me with using the SPA chambers and getting accustomed to equipment and the workings of the lab. who have also assisted me in numerous ways by their feedback and experimental support. Jesus Christ, my Lord and Savior, who had planned this period of time to refine me and cause me to know Him more. Abstract Within the brain, there are key feeding and locomotion circuits that feature the signaling of numerous peptides. Orexin A has been shown to have effects on feeding and physical activity behaviors when administered centrally or in several brain regions. This effect is site-specific and requires the presence of orexin receptors. Our lab has studied the behavioral effects of injecting orexin A into the dorsal rostral portion of the lateral hypothalamus. We have previously observed an acute increase in spontaneous physical activity as well as food intake following injection of orexin A into this area. The acute effect is also observed with bicuculline-mediated stimulation of neurons in the rostrolateral hypothalamus. It is likely that there are other peptide signaling systems which are downstream of orexin receptor activation in the rostrolateral hypothalamus that are responsible for the observed increase in spontaneous physical activity. In chapter one, we chose to study neurotensin signaling in the ventral tegmental area as a possible downstream event of orexin receptor activation in the rostrolateral …