Dopamine and insulin interact in the brain to control junk food cravings

A recent study published in Molecular Psychiatry suggests that compulsive eating is driven by a complex interaction between the brain’s reward system and metabolic signals, rather than a simple lack of willpower. Scientists discovered that dopamine receptors and insulin receptors work together in a specific brain region to act as a brake on the desire for highly palatable foods. These findings provide evidence that disruptions in this delicate balance make it harder to resist sugary and fatty foods, even when eating them has negative consequences.

Compulsive eating involves a strong urge to consume foods high in sugar and fat, even when a person is not physically hungry. Past research points to the involvement of the brain’s reward pathways, specifically the dopamine system, which helps regulate motivation and pleasure.

The dopamine D2 receptor is a specific protein on the surface of brain cells that receives dopamine signals and has been linked to obesity and addiction. Scientists noticed that these dopamine receptors are frequently located in the exact same spot as insulin receptors within the central amygdala. The central amygdala is a region deep in the brain that helps process emotions and motivation.

Insulin is a hormone well known for regulating blood sugar, but it also functions in the brain to help signal fullness. Because these two types of receptors were found together, the researchers designed a series of experiments to see if they interact. They aimed to find out how this potential crosstalk might control normal eating habits and contribute to harmful eating patterns.

“After publishing our 2018 PNAS study showing that dopamine D2 receptors in the central amygdala regulate impulsive behavior, we became increasingly curious about how this circuit might contribute to more persistent and maladaptive behaviors, such as compulsive-like eating. At the same time, most work on insulin signaling in the brain had focused on metabolism, with far less attention paid to how insulin might interact with reward and motivation circuits,” explained study author Ja-Hyun Baik, a professor at Korea University and head of the Molecular Neurobiology Laboratory.

The researchers first tested 12 normal male mice and 16 male mice genetically modified to lack dopamine receptors entirely. They trained the animals to press a lever to receive a sugary food pellet. Once the mice learned the task, the scientists added a mild electric foot shock alongside the food reward.

This setup measures compulsive behavior, as the mice had to decide if the sugary reward was worth an uncomfortable punishment. The normal mice tended to stop pressing the lever when the shocks began. The mice lacking dopamine receptors continued to press the active lever significantly more often. This indicates a high level of persistence in seeking the food reward despite the negative consequences.

Next, the scientists used specialized viral injections to safely alter the genes of another group of male mice. This procedure removed dopamine receptors exclusively in the central amygdala. They compared these specifically modified animals to a control group of mice with intact receptors. When subjected to the same lever-pressing task with foot shocks, the mice missing the receptors in the central amygdala again showed increased compulsive food-seeking.

To explore how the cells function, the researchers examined brain tissue from the mice. They found that removing dopamine receptors resulted in a roughly sixty percent drop in the number of insulin receptors in the central amygdala. This loss also impaired the normal chemical chain reaction that occurs inside the cell when insulin binds to its receptor.

“What surprised us most was how closely dopamine and insulin signaling interact in the brain,” Baik told PsyPost. “Despite insulin being present at relatively low levels in the brain, insulin receptors were highly expressed in the central amygdala and strongly co-localized with dopamine D2 receptors.”

The researchers then used a specific chemical compound to artificially activate the dopamine receptors. They found that stimulating the dopamine receptors directly increased the activation of the insulin receptors, even without extra insulin present. This suggests that dopamine activity actively enhances the brain’s sensitivity to insulin, which helps suppress the urge to keep eating.

To confirm the role of insulin, the scientists used a genetic technique to eliminate only the insulin receptors on cells that also contained dopamine receptors. Testing these newly modified male mice in the lever and foot shock task revealed the same pattern of behavior. Without insulin receptors on these specific cells, the animals demonstrated a robust increase in compulsive eating despite the shocks.

“At the molecular level, the effects we observed were modest,” Baik explained. “However, at the behavioral level, they were quite meaningful, particularly in situations involving conflict or negative consequences. Rather than producing an all-or-none change in eating, our manipulation specifically affected how persistent food-seeking behavior became under aversive conditions.”

“This suggests that D2 receptor–insulin receptor signaling in the central amygdala acts as a biological fine-tuner of motivation, rather than a simple on–off switch. In practical terms, this circuit appears to influence how hard it is to stop eating when one knows it may be harmful, which is a core feature of compulsive eating.”

The research team also measured the real-time activity of brain cells in living male mice using a fluorescent sensor. They observed that the activity of dopamine receptor cells in the central amygdala decreased when the mice consumed highly palatable food. The researchers then utilized optogenetics, a technique using targeted light to artificially turn specific brain cells on or off. Turning off these specific cells caused the mice to eat more of the sugary and fatty food.

Finally, the researchers used a specialized dopamine sensor to measure actual dopamine release in the brain while the animals ate. They allowed one group of modified mice unlimited access to the sugary, fatty food for two weeks. In mice with reduced dopamine receptors in the central amygdala, extended exposure to the rich diet led to a weakened dopamine signal. This provides evidence that lacking these receptors impairs the brain’s normal reward signaling during prolonged unhealthy eating.

“One important takeaway is that compulsive-like eating is not simply a matter of weak self-control or willpower,” Baik said. “Our findings suggest that eating behavior reflects an ongoing dialogue between metabolic signals, such as insulin, and dopamine systems in the brain.”

“In this context, insulin does more than regulate blood sugar, it also acts as a kind of “brake” on food-seeking behavior. Importantly, this brake works properly only when both systems are in balance. When dopamine signaling is disrupted, insulin has a harder time exerting its control, making it more difficult to resist highly palatable foods even when we are not physically hungry.”

“This may help explain why resisting certain foods can feel disproportionately difficult in some situations, even when we consciously want to stop,” Baik continued.

“Separately, this interaction may also offer insight into why insulin resistance is often observed in certain brain disorders, such as Parkinson’s disease or schizophrenia. Understanding how insulin and dopamine interact in the brain could eventually inform strategies for managing both metabolic and behavioral symptoms in these conditions.”

But as with all research, there are some caveats to consider regarding how these findings apply to humans.

“It is important to emphasize that this study was conducted in animal models using highly controlled and sophisticated genetic manipulations,” Baik noted. “Although many of the underlying biological pathways are conserved, human eating behavior is also shaped by complex social, psychological, and environmental factors. For that reason, we see this work as identifying a biological mechanism that contributes to vulnerability, rather than offering a complete explanation for compulsive eating in people.”

“While our findings point to a potentially important interaction between insulin and dopamine signaling in the brain, further studies in human systems will be needed to determine how this mechanism operates in health and disease.”

Future research will explore how these dopamine and insulin interactions operate across broader brain circuits. The scientists also plan to investigate how chronic stress or metabolic diseases alter this signaling balance. Exploring these pathways could help develop new strategies for managing both metabolic and behavioral symptoms in humans.

“This study highlights the value of breaking down traditional boundaries between metabolic and neuropsychiatric research,” Baik told PsyPost. “Behaviors such as compulsive eating sit at the intersection of these fields, and our findings show that hormones like insulin and neuromodulators such as dopamine each play multiple roles in the brain.”

“Importantly, it is not just their individual actions, but how these signals interact that ultimately shapes motivation and behavior. Our findings suggest that eating behavior is regulated not by a single hormone or neurotransmitter, but by the dynamic interplay between metabolic and dopaminergic signals that fine-tunes motivation.”

The study, “Dopamine D2 receptor modulation of insulin receptor signaling in the central amygdala: implications for compulsive-like eating behavior,” was authored by Bokyeong Kim, Minji Kim, Hyun-Yong Lee, Jung Hyun Pyo, Jihee Seo, Yoon Jeon, Ho Lee, Joung-Hun Kim, Seung Hyun Ahn, Sung Wook Chi, Je Kyung Seong & Ja-Hyun Baik.