Individual Susceptibility to Obesity: Psychological and Neurobiological Mechanisms
Derman, Rifka
2019
Abstract
Global obesity rates have been steadily rising for more than four decades and prevention of obesity has proven challenging. Obesity arises from chronic consumption of hypercaloric diets. Thus, treating and preventing obesity entails promoting adherence to energy appropriate diets. Yet this has proven challenging to the wider population, as is evident by the continually rising rates of obesity. Therefore, identifying factors that promote overeating is essential for the development of effective obesity treatment and prevention plans. Food-seeking and feeding behaviors depend on associative processes including instrumental and Pavlovian mechanisms. Another critical aspect mediating expression of these behaviors is the motivation that drives one to seek out and consume food. In recent years, studies in humans have highlighted the potential contribution of the motivational influence of cues associated with food to the obesity epidemic. In particular, studies have found that food cues elicit stronger brain responses in obese subjects and in normal weight people who subsequently gain more weight in the following year. These findings have led to the idea that enhanced responsiveness to Pavlovian stimuli associated with food may be a pre-existing trait that contributes to obesity susceptibility. The work presented in this dissertation examines the contribution of individual obesity susceptibility to the psychological and neurobiological mechanism underlying Pavlovian motivation. Using Pavlovian-to-instrumental transfer (PIT), a classic measure of Pavlovian motivation, in Chapters 2-4, I examine differences in the expression of PIT between obesity susceptible and non-susceptible rats. The results from these studies reveal that in selectively bred rats, obesity-prone rats exhibit stronger Single Outcome PIT (SO PIT) than obesity-resistant rats. Moreover, the expression of SO PIT in obesity-prone rats is mediated by calcium-permeable AMPA receptors (CP-AMPARs) in the Nucleus Accumbens (NAc) Core, but not in obesity-resistant rats. Similarly, in outbred rats the degree to which NAc Core CP-AMPARs contribute to SO PIT expression is strongly correlated with subsequent weight. Jointly these data demonstrate that Pavlovian motivation is enhanced in obesity-prone individuals and that NAc Core CP-AMPARs commonly mediated expression of SO PIT in both selectively bred obesity-prone rats and in outbred obesity susceptible rats. However, given that SO PIT does not distinguish between affective and sensory specific mechanisms of Pavlovian motivation, I subsequently compared the expression of Sensory Specific PIT (SS PIT) versus General PIT in selectively bred and outbred populations. These data reveal that obesity-prone rats exhibit enhanced General PIT versus obesity-resistant rats and that in outbred rats the magnitude of General PIT is strongly positively associated with subsequent weight. This finding explicitly identifies enhanced affective Pavlovian motivation as the primary driver of enhanced PIT in susceptible individuals, prior to obesity. Chapters 5-6 examined factors that contribute to Pavlovian motivation independent of obesity susceptibility. In Chapter 5, I show that post-training consumption of a palatable ‘Junk-Food’ diet enhances conditioned food cup approach, independent of individual susceptibility. In Chapter 6, I demonstrate that the expression of SS PIT depends critically on CamKII Basolateral Amygdalar (BLA) neurons. Collectively, the work presented in this dissertation provides preclinical evidence that obesity susceptibility is accompanied by pre-existing enhancements in Pavlovian motivation which depends on unique neurobiological mechanisms in susceptible versus resistant populations. Moreover, independent of obesity susceptibility, experience with palatable diets can enhance Pavlovian motivation. In summary, the data in this dissertation identify extrinsic and intrinsic factors contribute to Pavlovian motivational processes.Subjects
Pavlovian Motivation Obesity Susceptibility CP-AMPARs Nucleus Accumbens Amygdala Pavlovian-to-Instrumental Transfer
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