Role of the Striatum in Obesity

Research performed at the University of Michigan is helping to determine how cue-triggered motivational responses differ both before and after the onset of obesity, and how these responses can be linked to a difference in striatal function between obese and non-obese populations.

According to lead investigator Carrie Ferrario, PhD, “Obesity is a very complicated problem, and it has very different contributing factors.” Various stimuli are believed to influence our eating behaviors and can encourage us to eat larger portions, as well as encourage us to make food choices that we ordinarily might not. Obese people tend to be more sensitive to the motivational properties of food. The University of Michigan researchers hypothesized that enhanced cue-trigger urges might contribute to overall food consumption and drive the development of obesity.

The integration of dopamine and glutamate is essential in activating the striatum, and the magnitude of this response, stronger in the obese, can predict future weight gain and poor weight loss outcomes. Dr Ferrario feels that the evidence suggests that there are differences in the function of the striatum both before and after the development of obesity.

She and her colleagues completed their study on two groups of rats selectively bred for both obesity and resistance to obesity. This research focused on changes in the nucleus accumbens (NAc), an area of the brain increasingly being associated with obesity. The calcium permeable AMPA receptors (CP-AMPARs) in this region are critical to responses for motivation and reward. Her research helped corroborate a previous finding that eating highly palatable, junk-type foods enhances excitatory transmission in the NAc and is mediated by the AMPA receptors; blocking the transmission of the AMPA receptors prevented the cue-triggered food-seeking behaviors by the obese animals but had only a weak effect on this behavior in the obesity-resistant group. She specifically observed a 30% up-regulation of AMPA receptors in the obesity-prone group in response to eating palatable foods. Moreover, these increases occurred prior to the diagnosis of obesity.

Her conclusions validated previous research in this area (Robinson, et al. Neuropsychopharmacology 2015), showing that up-regulation contributes to behavior and occurs more readily in obesity-prone rats, driving over-consumption.¹ Conversely, blocking the CP-AMPARs was sufficient to block the behavior in these animals. Dr. Ferrario concluded, “cue-triggered food-seeking is stronger in obesity- prone rats as compared to obesity-resistant rats and this is happening before any overt dysregulation.” She further expounded, “experience with things like junk food and PIT training are sufficient to increase CP-AMPARs in the NAc.”

In summary, the research data of Dr Ferrario and her colleagues supports the idea of basal differences in cue-triggered motivation and suggests that cue-triggered motivational responses may contribute to the development of obesity in susceptible individuals. Striatal function differs in obese versus non-obese individuals and shows a plasticity from before and after the development of obesity. Further research investigating these neural mechanisms and plasticity can be used to direct treatment development.

Session S09: Where is the Sweet Tooth? Mechanisms Governing Palatable Intake and Weight Gain. ENDO 2017 annual meeting, Orlando, FL. April 1, 2017

1. Robinson MJ, et al. Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity. Neuropsychopharmacology. 2015 Aug;40(9):2113-2123.