Hunger is a basic sensation that drives organisms to seek food and sustain life. But did you ever wonder what triggers that sensation? Or how the brain regulates it?.

Researchers at the Albert Einstein College of Medicine, New York, discovered a fascinating mechanism that links hunger to the brain’s reward system.

In this article, we will explore that mechanism, its implications, and potential therapeutic applications.

What is Hunger?

Hunger is the physiological response to a nutrient deficit or an energy shortage in the body. It is regulated by a complex interplay between hormonal, neurological, and environmental factors.

The primary hormone that signals hunger is ghrelin. Produced in the stomach, ghrelin increases appetite and slows metabolism to conserve energy.

Other hormones, such as leptin, insulin, and cortisol, also contribute to hunger regulation by signaling satiety, glucose levels, and stress.

The brain receives these hormonal signals and integrates them with other sensory and cognitive inputs to generate the sensation of hunger. But where exactly in the brain does that happen?.

The Hypothalamus and the Reward System

The hypothalamus is a small but crucial region in the brain that controls many autonomic functions, including hunger and thirst.

It contains specialized neurons that respond to hormonal and nutrient signals and project to other brain areas to orchestrate the feeding behavior.

One of these brain areas is the mesolimbic dopamine system, or the reward system, which is involved in motivation, pleasure, and addiction.

The reward system is triggered by natural or artificial stimuli, such as food, sex, drugs, or gambling, that increase dopamine release in the brain.

Previous studies have shown that the dopamine system also responds to food cues and predicts food availability, suggesting its involvement in hunger and eating behavior.

However, the specific neuronal circuits and mechanisms that link the hypothalamus and the reward system were not clear.

The Experiments: Optogenetics and Feeding Behavior

To investigate the neuronal circuits that control hunger and the reward system, the researchers used optogenetics, a genetic and optical technique that allows them to selectively activate or inhibit neurons in live animals.

They targeted a group of hypothalamic neurons called AgRP neurons, which are known to promote feeding behavior by releasing neuropeptides that stimulate appetite and reduce metabolism.

They also targeted a group of dopamine neurons in the ventral tegmental area (VTA), a brain region that contains the nucleus accumbens, a key component of the reward system.

The researchers used genetically modified mice that expressed light-sensitive proteins in these neurons and inserted fiber-optic wires into their brains to deliver light pulses that activate or inhibit the neurons.

They trained the mice to perform a behavioral test that measures their preference for food over water.

The test consisted of two chambers, one with food pellets and the other with water, connected by a central corridor.

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The mice were free to move between the chambers, and the researchers recorded their activity and feeding behavior while manipulating the AgRP and VTA neurons with light stimulation.

The Results: Hunger and Reward Signals

The optogenetic experiments revealed a surprising finding: the AgRP neurons not only promote feeding behavior but also inhibit the dopamine neurons in the VTA.

When the AgRP neurons were activated, the dopamine neurons were silenced, and the mice showed a strong preference for food over water.

In contrast, when the researchers inhibited the AgRP neurons, the dopamine neurons were disinhibited, and the mice showed a weaker preference for food over water.

These results suggest a negative feedback loop between the hypothalamus and the reward system that regulates hunger.

When the AgRP neurons are activated by hormonal or metabolic signals, they stimulate feeding behavior and simultaneously inhibit the dopamine neurons to reduce the reward expectation and prevent overeating.

Conversely, when the AgRP neurons are inhibited, the dopamine neurons are disinhibited, which increases the reward expectation and reduces the drive for food intake.

This mechanism might explain why some people lose their appetite in stressful or emotional situations, where the reward system is activated by other stimuli.

Clinical Implications and Therapeutic Applications

The discovery of the hypothalamus-reward system mechanism has significant implications for understanding and treating eating disorders, obesity, and addiction.

For instance, patients with anorexia nervosa, a severe eating disorder characterized by a distorted body image and fear of gaining weight, show altered activity patterns in the reward system and the hypothalamus.

By targeting the AgRP neurons and the dopamine neurons with optogenetics or drugs, researchers might be able to restore the balance between hunger and reward signals and alleviate anorexia symptoms.

Similarly, patients with obesity or binge-eating disorder, who experience dysregulated hunger and satiety signals and overeat, could benefit from therapies that modulate the hypothalamus-reward system mechanism.

By reducing the reward expectation and increasing the satiety signals, these therapies might help patients reduce their caloric intake and maintain a healthy weight.

Lastly, patients with drug or alcohol addiction, who also show altered reward signals and hypothalamic activity, could benefit from therapies that target the same mechanisms.

By reducing the reward expectation and increasing the inhibitory signals, these therapies might help patients overcome their cravings and reduce their drug intake.

Conclusion

The discovery of the hypothalamus-reward system mechanism that controls hunger is a significant breakthrough in neuroscience and medicine.

By unraveling the complex neuronal circuits and feedback loops that regulate feeding behavior, researchers can develop novel therapies for eating disorders, obesity, and addiction.

Moreover, the study highlights the interdependence between hormonal and neurological signals and the intricate balance that maintains homeostasis in the body. Understanding and respecting that balance is crucial for our health and well-being.