|Funding Agency||National Institutes of Health|
|Funding Mechanism||OTHER RESEARCH-RELATED|
Obesity is a major concern for our society, and development of strategies to help decrease body weight is important in the battle against obesity and comorbid health conditions. As the major endogenous mechanism responsible for combating obesity, understanding how proopiomelanocortin (POMC) mediates feeding and reward learning, and how this may change following obesity is essential for rational development of therapeutics to treat obesity. Neurons containing POMC are found in the arcuate nucleus and project to many areas such as the nucleus accumbens and hypothalamus. Beta-endorphin (b-END) and alpha-melanocyte stimulating hormone (a-MSH) are neuropeptide products of POMC, and have well-established central roles in reward (food, drugs of abuse, sex) and learning. Despite their hypothesized co-release from terminals, studies to date have overwhelmingly looked at the role of either b-END or a-MSH alone in feeding and reward, and results from these studies have suggested opposing roles for these peptides in feeding which is perplexing. The overall objective for this application is to 1) determine sensitivity of nucleus accumbens projecting POMC neurons to leptin and insulin (known simulators of POMC neuron firing), and 2) establish the physiological and behavioral role of co- released b-END and a-MSH in the nucleus accumbens in feeding and reward learning. These two objectives will be assessed in energy neutral state and following diet induced obesity to assess if adaptations to the system occur following obesity. The central hypothesis is that POMC signaling in the nucleus accumbens is important in the regulation of feeding and learning about food reward, and that this role for POMC is impaired following development of obesity. These studies will, for the first time, delineate the behavioral role of POMC signaling from the arcuate nucleus to the nucleus accumbens on reward learning and feeding both in normal energy state and after the development of obesity.
Relevance: The studies proposed will establish the role of POMC peptides in feeding and reward learning, and establish the behavioral role of co-release of b-END and a-MSH in the nucleus accumbens. An understanding of the role of this neurocircuitry in feeding and reward learning, both in a healthy state and following development of obesity, is essential for rational design of therapeutics to treat obesity.