Obesity and cognitive dementia may seem to have little in common other than both can have severe health consequences and both have so far been highly resistant to therapeutic interventions. Traditionally, investigators have viewed the problems of obesity and metabolic syndrome, on one hand and cognitive dementia on the other, as involving distinct etiologies, that target different underlying behavioral and biological functions, and that rely on largely separate brain structures and circuits. However, recent epidemiological findings point to a link between obesity in mid-life and the emergence of Alzheimer's disease and other serious cognitive impairments in the aged. These findings have encouraged the hypothesis that obesity may be causally-linked to cognitive impairment. Using a rodent model, this present project will explore (the perhaps counter-intuitive) idea that excessive energy intake leading to obesity and related metabolic disorders (e.g., diabetes, hypertension) is a consequence of interference with learning and memory processes. Based on the results of prior support for our work, we have developed a model that describes the learning and memory mechanisms that underlie the ability of animals, including humans, to use internal cues corresponding to """"""""satiety"""""""" to signal when food and cues related to food will be followed by appetitive or desirable postingestive ( i.e., post oral) stimulation. Our research indicates that this type of signaling can be degraded by (1) the consumption of sweet no- or reduced-calorie foods/fluids that may weaken t he normally strong predictive relationship between the orosensory properties of food and the caloric or nutritive consequences of eating;(2) consuming diets that impair the functioning of a brain structure (i.e., the hippocampus) that underlies the ability of rats to use their satiety cues to predict when eating food will or will not produce reinforcing postingestive outcomes. A result of degrading the operation of these learning mechanisms is excess intake and body weight. The present research will examine whether learned control mechanisms develop without explicit laboratory training, whether consumption of high-fat diets interferes with these mechanisms, and whether this interference has potential to produce significant weight gain. These studies promise to yield important new information about the role of dietary factors in both obesity and cognitive decline.

Public Health Relevance

Obesity and cognitive decline are both serious threats to the public health and to the of quality life. This project will explore the possibility that both of these disorders have common environmental origins and brain substrates. The idea that disruption in a specific learning process gives rise to obesity will also be examined.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Grave, Gilman D
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American University
Schools of Arts and Sciences
United States
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Jones, Sabrina; Sample, Camille H; Hargrave, Sara L et al. (2018) Associative mechanisms underlying the function of satiety cues in the control of energy intake and appetitive behavior. Physiol Behav 192:37-49
Sample, Camille H; Jones, Sabrina; Hargrave, Sara L et al. (2016) Western diet and the weakening of the interoceptive stimulus control of appetitive behavior. Behav Brain Res 312:219-30
Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L (2016) The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction. Curr Opin Behav Sci 9:40-46
Hargrave, Sara L; Davidson, Terry L; Zheng, Wei et al. (2016) Western diets induce blood-brain barrier leakage and alter spatial strategies in rats. Behav Neurosci 130:123-35
Sample, Camille H; Martin, Ashley A; Jones, Sabrina et al. (2015) Western-style diet impairs stimulus control by food deprivation state cues: Implications for obesogenic environments. Appetite 93:13-23
Hargrave, Sara L; Davidson, Terry L; Lee, Tien-Jui et al. (2015) Brain and behavioral perturbations in rats following Western diet access. Appetite 93:35-43
Davidson, Terry L (2014) Do impaired memory and body weight regulation originate in childhood with diet-induced hippocampal dysfunction? Am J Clin Nutr 99:971-2
Davidson, Terry L; Tracy, Andrea L; Schier, Lindsey A et al. (2014) A view of obesity as a learning and memory disorder. J Exp Psychol Anim Learn Cogn 40:261-79
Martin, Ashley A; Davidson, Terry L (2014) Human cognitive function and the obesogenic environment. Physiol Behav 136:185-93
Davidson, T L; Sample, C H; Swithers, S E (2014) An application of Pavlovian principles to the problems of obesity and cognitive decline. Neurobiol Learn Mem 108:172-84

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