Obesity has reached a crisis point in the Western world, especially in the US where one third of the population is obese, and many more are classified as overweight. A major cause of obesity is overeating, the majority of which is targeted to energy-dense, highly palatable foods. Feeding is the product of a complex interaction between humoral, metabolic, physiological and psychological processes. Regarding the latter, advances in the neurobiology of motivated behavior and addiction demonstrate that endogenous opioid peptides and dopamine are central to affective processing of rewarding stimuli, especially food, and to learning about rewards and the relevance of reward-related stimuli, making them logical suspects for focused investigation in the etiology of obesity. In the first part of this project, we will test the hypothesis that chronic consumption of energy-dense highly palatable foods disrupts opioid-dependent instrumental incentive learning processes, resulting in discordance between the pleasurable experience of palatable food consumption and the incentive value assigned to the food that guides food-seeking behavior, leading ultimately to compulsive food-seeking. The hypothesized role of disruption in endogenous opioid transmission in the basolateral amygdala will be tested using a combination of pharmacological and genetic interventions and by measurement of enkephalin release. As environmental stimuli, such as carefully engineered advertising, packaging and product placement can potently influence feeding, the second part of the project will test the hypothesis that chronic consumption of highly palatable foods accentuates cue-induced food-seeking, and that this process involves plasticity in central dopamine and/or opioid transmission. Thus, we will combine a preclinical model of diet-induced obesity with a combination of advanced behavioral, neurochemical and genetic methodologies to yield data that promise to have important implications for guiding public policy and treating overeating and obesity.
This project will study the effect, in rodents, of long-term consumption of a highly palatable Western-style diet on behavioral mechanisms controlling the pursuit of palatable foods. The project also will examine the neurochemical underpinnings of such behavior. The results of this study will have important implications for treating overeating and obesity.
|Kosheleff, Alisa R; Araki, Jingwen; Hsueh, Jennifer et al. (2018) Pattern of access determines influence of junk food diet on cue sensitivity and palatability. Appetite 123:135-145|
|Ostlund, Sean B; Cui, Yijun (2018) Not worth the wait: cocaine alters reward processing in the nucleus accumbens. Neuropsychopharmacology 43:2333-2334|
|Kosheleff, Alisa R; Araki, Jingwen; Tsan, Linda et al. (2018) Junk Food Exposure Disrupts Selection of Food-Seeking Actions in Rats. Front Psychiatry 9:350|
|Marshall, Andrew T; Halbout, Briac; Liu, Angela T et al. (2018) Contributions of Pavlovian incentive motivation to cue-potentiated feeding. Sci Rep 8:2766|
|Ostlund, Sean B; Liu, Angela T; Wassum, Kate M et al. (2017) Modulation of cue-triggered reward seeking by cholinergic signaling in the dorsomedial striatum. Eur J Neurosci 45:358-364|
|Collins, Anne L; Aitken, Tara J; Greenfield, Venuz Y et al. (2016) Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation. Neuropsychopharmacology 41:2830-2838|
|Murphy, Niall P (2015) Dynamic measurement of extracellular opioid activity: status quo, challenges, and significance in rewarded behaviors. ACS Chem Neurosci 6:94-107|