Stress Changes Feeding Behavior in Mice. What About People?

• A study on mice published in the Frontiers in Neuroscience found that their feeding behavior changes when exposed to stress.
• Stressed mice tended to fixate on a single source of food, deviating from the natural tendency of mice to try different sources when they are available.
• This behavior could be artificially caused by inhibiting the activity of dopaminergic neurons going from the ventral tegmental area to the nucleus accumbens shell area of the brain while injecting dopamine in the later area would eliminate it.

Many people experience stress that can affect their behavior related to food. Extreme stress can cause us to lose our appetite and “forget to eat.” However, stress can sometimes also make us want to eat, very often snacks and different highly palatable foods (e.g., sweets, chocolates). To describe this and similar phenomena, scientists coined the term emotional eating.

 

Stress can sometimes also make us want to eat, very often snacks and different highly palatable foods.

 

Emotional eating
Emotional eating is a “tendency to eat in response to negative emotions with the chosen foods primarily being energy-dense and palatable” (Konttinen, 2020; Ljubičić et al., 2023). People engage in emotional eating in response to feelings like stress, sadness, boredom, or anxiety. Sometimes, even positive emotions like happiness can trigger the desire to eat. This behavior often involves craving high-calorie comfort foods (such as sweets or junk food), leading to unhealthy eating patterns and potential weight gain (Dakanalis et al., 2023).

 

People engage in emotional eating in response to feelings like stress, sadness, boredom, or anxiety. Sometimes, even positive emotions like happiness can trigger the desire to eat.

 

However, the link between food consumption, emotions, and mood in general is much broader. For example, a recent study reported that individuals tend to report greater anger, irritability, and decreased pleasure when hungry (Swami et al., 2022). In animals, hunger increases their motivation to engage in escalated and persistent aggression to acquire food. Keepers of animals know very well that the animals are the most dangerous when hungry. This link between negative emotions and hunger gave rise to the term “hangry,” describing a state in which one experiences hunger and anger due to hunger (Hedrih, 2023; Swami et al., 2022).

 

In animals, hunger increases their motivation to engage in escalated and persistent aggression to acquire food. 

 

The neural basis of food-seeking behaviors
Food-seeking behaviors are complex activities regulated by various areas of the brain, including those responsible for the most complex behaviors. However, studies indicate that the hypothalamus is the primary area of the brain regulating these behaviors.

It is the part of the brain where agouti-related peptide (AgRP) neurons, also known as “hunger neurons,” are located. Experiments on rodents revealed that triggering the activity of these neurons makes the animals start eating but also produces anti-inflammatory effects (Hedrih, 2024a; Klima et al., 2023). Another more recent study identified a group of neurons in the midbrain projecting to the hypothalamus (vesicular GABA transporter-expressing GABAergic neurons), the activity of which alone triggers food-seeking behaviors in rodents (Hedrih, 2024b; Reis et al., 2024).

Another component regulating this complex behavioral mechanism is neurons utilizing the neurotransmitter dopamine located in the nucleus accumbens region of the brain and interacting with the hypothalamus. These neurons are part of the brain’s reward system, processing feelings of reward, pleasure, or cravings related to food (Aitken et al., 2016) (see Figure 1).

 

Figure 1. Neural Pathways Driving Food-Seeking Behavior

 

The current study
Study author Yusuke Fujioka and his colleagues wanted to investigate how stress affects feeding behaviors in mice and identify physiological and neural mechanisms responsible for these changes (Fujioka et al., 2024).

These authors conducted a series of experiments on wild-type C57BL/6J strain mice. This is an inbred strain of laboratory mice commonly used in research studies due to its consistent genetic background and well-documented physiology. They also used two other strains of mice, genetically engineered to allow researchers to control and track the activity of neurons in their brains that produce the neurotransmitter dopamine (Dopamine transporter (DAT)-Cre mice and Tyrosine hydroxylase (TH)-Cre mice).

In each experiment, mice were divided into an experimental and a control group. The experimental groups were subjected to various stressors, including social isolation (through solitary housing), limited access to food (access to a high-fat diet for 2 hours per day only), and restraint (mice were completely immobilized in a special device for 2 hours on five consecutive days). Control groups lived with free access to food and water without exposure to these stressors.

After the treatments, the authors ran behavioral experiments that monitored these mice’s feeding behaviors. They also monitored levels of the neurotransmitter dopamine in the nucleus accumbens shell regions of their brains and performed surgery on some of the mice from the experimental groups, allowing them to administer dopamine to this region of their brains (see Figure 2).

 

Figure 2. Study Procedure (Fujioka et al., 2024)

 

Stress leads to fixated eating
Normally, when exposed to multiple food sources, mice try food from all of them and explore the available food sources. However, mice exposed to stress tended to fixate on one of the food sources, eating mainly from it while devoting little time to exploring the other sources.

Stress impairs the release of dopamine in the nucleus accumbens shell
10-30 minutes after feeding, dopamine levels in the nucleus accumbens shell of mice from the control groups would increase. However, this increase was absent in mice exposed to stress (socially isolated mice) or much lower (other experimental groups). The nucleus accumbens shell is a subregion of the nucleus accumbens that plays a critical role in regulating motivation for food (among other things).

When the study authors injected dopamine directly into the nucleus accumbens shells of the experimental group mice, fixated eating stopped, and their feeding behavior returned to normal. This confirmed that the reduced release of dopamine produced changes in feeding behavior.

Finally, the study authors used specific drugs to inhibit the activity of neurons that produce and release dopamine from the brain’s ventral tegmental area to the nucleus accumbens shell in their genetically engineered mice. This reduced dopamine levels in the nucleus accumbens shells of these mice and changed their feeding behavior so that they also displayed fixated eating (see Figure 3).

 

Figure 3. Stress impairs the release of dopamine in the nucleus accumbens shell

 

Conclusion
The study discovered a mechanism through which stress affects feeding behaviors in mice. Feeding behaviors in humans are more complex than in mice, but neural mechanisms are often not too dissimilar in the two species. Because of this, mapping neural circuits and mechanisms controlling feeding behavior in mice will help scientists better understand and study food-related behaviors in humans.

The paper “Stress-impaired reward pathway promotes distinct feeding behavior patterns” was authored by Yusuke Fujioka, Kaori Kawai, Kuniyuki Endo, Minaka Ishibashi, Nobuyuki Iwade, Dilina Tuerde, Kozo Kaibuchi, Takayuki Yamashita, Akihiro Yamanaka, Masahisa Katsuno, Hirohisa Watanabe, Gen Sobue, and Shinsuke Ishigaki.

 

References

Aitken, T. J., Greenfield, V. Y., & Wassum, K. M. (2016). Nucleus accumbens core dopamine signaling tracks the need-based motivational value of food-paired cues. Journal of Neurochemistry, 136(5), 1026–1036. https://doi.org/10.1111/jnc.13494

Dakanalis, A., Mentzelou, M., Papadopoulou, S. K., Papandreou, D., Spanoudaki, M., Vasios, G. K., Pavlidou, E., Mantzorou, M., & Giaginis, C. (2023). The Association of Emotional Eating with Overweight/Obesity, Depression, Anxiety/Stress, and Dietary Patterns: A Review of the Current Clinical Evidence. Nutrients, 15(5), 1173. https://doi.org/10.3390/nu15051173

Fujioka, Y., Kawai, K., Endo, K., Ishibashi, M., Iwade, N., Tuerde, D., Kaibuchi, K., Yamashita, T., Yamanaka, A., Katsuno, M., Watanabe, H., Sobue, G., & Ishigaki, S. (2024). Stress-impaired reward pathway promotes distinct feeding behavior patterns. Frontiers in Neuroscience, 18, 1349366. https://doi.org/10.3389/fnins.2024.1349366

Hedrih, V. (2023). Food and Mood: Is the Concept of ‘Hangry’ Real? CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/food-and-mood-is-the-concept-of-hangry-real/

Hedrih, V. (2024a, March 4). Researchers Identify Neural Pathways Transmitting Anti-Inflammatory Effects of Hunger. Nutritional Psychology. https://www.nutritional-psychology.org/researchers-identify-neural-pathways-transmitting-anti-inflammatory-effects-of-hunger/

Hedrih, V. (2024b, September 16). Study Identifies Neurons Controlling Food-Seeking Behaviors in Mice. CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/study-identifies-neurons-controlling-food-seeking-behaviors-in-mice/

Klima, M. L., Kruger, K. A., Goldstein, N., Pulido, S., Low, A. Y. T., Assenmacher, C. A., Alhadeff, A. L., & Betley, J. N. (2023). Anti-inflammatory effects of hunger are transmitted to the periphery via projection-specific AgRP circuits. Cell Reports, 42(11). https://doi.org/10.1016/j.celrep.2023.113338

Konttinen, H. (2020). Emotional eating and obesity in adults: The role of depression, sleep and genes. Proceedings of the Nutrition Society, 79(3), 283–289. https://doi.org/10.1017/S0029665120000166

Ljubičić, M., Matek Sarić, M., Klarin, I., Rumbak, I., Colić Barić, I., Ranilović, J., Dželalija, B., Sarić, A., Nakić, D., Djekic, I., Korzeniowska, M., Bartkiene, E., Papageorgiou, M., Tarcea, M., Černelič-Bizjak, M., Klava, D., Szűcs, V., Vittadini, E., Bolhuis, D., & Guiné, R. P. F. (2023). Emotions and Food Consumption: Emotional Eating Behavior in a European Population. Foods, 12(4), Article 4. https://doi.org/10.3390/foods12040872

Reis, F. M. C. V., Maesta-Pereira, S., Ollivier, M., Schuette, P. J., Sethi, E., Miranda, B. A., Iniguez, E., Chakerian, M., Vaughn, E., Sehgal, M., Nguyen, D. C. T., Yuan, F. T. H., Torossian, A., Ikebara, J. M., Kihara, A. H., Silva, A. J., Kao, J. C., Khakh, B. S., & Adhikari, A. (2024). Control of feeding by a bottom-up midbrain-subthalamic pathway. Nature Communications, 15(1), 2111. https://doi.org/10.1038/s41467-024-46430-5

Swami, V., Hochstöger, S., Kargl, E., & Stieger, S. (2022). Hangry in the field: An experience sampling study on the impact of hunger on anger, irritability, and affect. PLOS ONE, 17(7), e0269629. https://doi.org/10.1371/JOURNAL.PONE.0269629