Date of Award
Doctor of Philosophy (PhD)
Harvey J. Grill
Matthew R. Hayes
Obesity is chronic and recurring disease of energy balance and metabolism whose prevalence, cost, and associated negative health outcomes necessitate development of effective treatment. Given that energy balance and food intake are regulated in the central nervous system, the development of treatment relies on basic science investigations of the neuroendocrine controls of feeding and the neural hubs that modulate this control, including the nucleus tractus solitarius (NTS) in the caudal hindbrain. As such, this dissertation investigates the neurobehavioral mechanisms contributing to alterations in food intake driven by caudal hindbrain acting signals as well as investigations of neurobehavioral individual differences in responsivity to a subset of these signals as risk factors for the development of obesity. Chapter 1 investigated an additional mechanism contributing to oxytocin (OT)-induced intake inhibition, finding that, in addition to amplifying the effects of GI satiation signals, OT reduced aspects of appetitive control including food motivation and food seeking when applied ICV but also to the NTS and to the midbrain ventral tegmental area (VTA). The studies presented in chapter 2 investigated the neurobehavioral mechanisms of ghrelin induced intake stimulation in the hindbrain and show that ghrelin increases food intake by attenuating both the neural and behavioral effects of the GI satiation signal cholecystokinin (CCK) but does not impact food motivation or food seeking. The data presented in chapter 3 show that individual differences in responsivity to CCK predict subsequent diet-induced obesity, such that rats with reduced CCK sensitivity, gain more weight when maintained on a high fat high sugar (HFHS) diet than rats with greater CCK-induced intake inhibition. Together, the data in this dissertation further the understanding of the neurobehavioral mechanisms contributing to alterations in food intake by caudal hindbrain acting signals as well as provides novel insights into how individual differences in sensitivity to these signals themselves are risk factors for the development of obesity.
Wald, Hallie Sage, "Neurobehavioral Mechanisms Contributing To Alterations In Food Intake Driven By Caudal Hindbrain Acting Signals" (2021). Publicly Accessible Penn Dissertations. 4704.