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Insulin signaling in the brain influences behavior, weight regulation, motivation, and cognition. Previous research demonstrates that insulin resistance reduces brain volume and cognitive function in middle-aged adults. Results of a new study demonstrate that insulin interacts with dopamine to modulate reward-based behavior and whole-body metabolism.

Dopamine is a neurotransmitter that regulates activity of the mesocorticolimbic system, a region of the brain involved in reward-based learning. Mesocorticolimbic circuits transmit information from the midbrain to the ventral and dorsal striatum, prefrontal cortex, amygdala, and hippocampus to coordinate emotions, memories, and impulses involved in eating and other rewarding behaviors. Previous research has demonstrated that insulin interacts with dopamine, altering activity of the mesocorticolimbic systems, inducing feelings of satiety and decreasing high-calorie food seeking. However, much of the existing research has been conducted in mice, using very high levels of insulin, making translation to humans difficult.

The investigators assigned ten male participants (average age, 27 years) with a normal BMI (average BMI, 24) to receive either intranasal insulin or a placebo and undergo a combined PET and MRI scan after having fasted overnight. The researchers gave participants an injection of a radioactive marker called [11C]-raclopride that binds to dopamine receptors so they could measure dopamine-related brain activity during the scan. Participants also completed surveys to assess eating behavior and provided a blood sample for measurement of insulin and other hormones.

Following administration of intranasal insulin, [11C]-raclopride synaptic binding potential increased in the ventral and dorsal striatum, suggesting an increase in the number of dopamine receptors in these regions. Accordingly, synaptic dopamine concentrations (dopamine that has not bound to a receptor and internalized by the neuron) decreased. Ultimately, this increase in dopamine signaling reduced resting-state activity in the ventral and dorsal striatum and improved functioning of mesocorticolimbic circuits 15 to 45 minutes after insulin exposure. As the participants' response to insulin exposure increased, so did their scores on tests of subjective wellbeing and cognitive control.

This study, which demonstrated the effects of intranasal insulin on dopamine activity in the mesocorticolimbic system, has important implications for reward-based learning, eating behavior, and obesity. Future research should include participants with insulin resistance to gain a better understanding of the effects of obesity and metabolic disease on the brain.

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