Reward And Unease Are Closely Linked in The Brain


Source: Linköping University

Summary: According to a new study, mice that lack a certain receptor in the brain are attracted to situations associated with discomfort, such as inflammation and nausea.


The brains of both humans and other animals have circuits that connect powerful impressions from the senses to positive or negative feelings – a function that is necessary for survival. These circuits drive the organism to seek things that increases the probability of survival and reproduction, such as food and sex, since these produce pleasure. Along the same line, the evaluation helps animals to avoid harmful things and situations, linked to feelings of unease and depression. The signal circuits in the brain that regulate our experience of positive and negative are also activated by disease. During long-term diseases, such as chronic inflammatory diseases, cancer and depression, the system can cause huge suffering by negatively affecting motivation and mood. Researchers from the Linköping University found a mice that lack a certain receptor in the brain is attracted to situations associated with discomfort, such as inflammation and nausea. The study findings were published in the Journal of Clinical Investigation.

Melanocortin 4 receptor

David Engblom’s research group at Linköping University investigates the mechanisms in the brain underpinning the negative affective states associated with different diseases. Credit: Thor Balkhed/Linköping University

In the new study, the researchers were interested in a specific type of receptor, the melanocortin 4 receptor, found on certain nerve cells. They studied mice that lacked melanocortin 4 receptors and examined how the animals reacted to inflammation. Normal mice avoid an environment that they associate with becoming sick, if they can choose between it and another place. Mice that lack the melanocortin 4 receptor behave in the opposite manner, and are attracted to such environments, as if they liked the inflammation. One of the key components of the reward system is the signal substance dopamine, which acts as a chemical messenger between nerve cells. Dopamine stimulates motivation and causes animals and humans to exert themselves to achieve anything that is experienced as rewarding.

When the researchers examined the dopamine-based signalling in the brain, they saw that the dopamine level in normal mice fell in the reward centre of the brain when the animals experienced something unpleasant. In contrast, it increased slightly in the mice that lacked melanocortin 4 receptors.

Assoc. Prof. David Engblom said, “It seems that this receptor in some way prevents danger signals from activating the reward system. If the receptor is missing, the danger signals will gain access to the reward system and activate it. This means that mice that lack the receptor will seek out things that are associated with danger or discomfort.”


More Information: Anna Mathia Klawonn et al, “Motivational valence is determined by striatal melanocortin 4 receptors”, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI97854 


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