Medical Student Research Fellowship for Summer 2007

Mentor: Jeffrey M. Zigman, M.D., Ph.D.
Department: Internal Medicine / Endocrinol and Metabol, Hypothalamic Resrch
Room number: Y6314C
Mail Code: 9077
Phone number: 214-648-6422
E-mail: jeffrey.zigman@utsouthwestern.edu
Project title: Ghrelin and Food Reward

Human subjects IRB approved project number (where applicable): N.A.

Animal subjects IRB approved project number (where applicable): 2008-0107

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) animal-based research

Brief Description of Project:

Ghrelin is a hormone with diverse actions, the most studied of which are its effects on body weight homeostasis. For instance, ghrelin levels rise in association with hunger and fasting. Also, ghrelin stimulates food intake, decreases energy expenditure, and induces obesity when present in high concentrations. Ghrelin's actions are mediated by interaction with its receptor, the growth hormone secretagogue receptor (GHSR; ghrelin receptor), which has a well-defined, discrete pattern of expression within the brain. This includes a high degree of expression in dopamine-containing neurons within a part of the brain known as the ventral tegmental area (VTA). These dopaminergic VTA neurons have been highly studied due to their involvement in brain reward circuits, such as those associated with addiction. The current project includes a series of experiments designed to increase our understanding of the involvement of ghrelin in promoting reward-seeking behaviors aimed at obtaining food and the role of the VTA in ghrelin action. To accomplish this, unique mouse models in which either expression of the ghrelin receptor has been deleted or the functioning of the ghrelin receptor has been blocked by the administration of a specific antagonist will be used. These mice will be subjected to a battery of tests that will allow us to determine the effect of genetic and pharmacological blockade of ghrelin signaling pathways on food-reinforced reward-seeking behaviors. Also, a unique mouse model in which ghrelin receptor expression can be selectively targeted to dopaminergic VTA neurons will be used in order to investigate the sufficiency of ghrelin's engagement of these particular neurons for its actions on reward behaviors and body weight. It is hoped that these studies will result in new targeted therapies to treat the unrelenting food-seeking behaviors characteristic of certain forms of obesity, such as Prader-Willi Syndrome, as well as other maladaptive reward behaviors, such as those associated with addiction.

Previous Research Activities or Publications with Medical Students:

My most recent mentoring experience has been with postdoctoral fellows. Although I have worked alongside medical students on numerous publications in the past, those prior interactions were not as mentor.