The human brain has circuits that convert impressions from the senses to positive or negative feelings. These circuits push the brain to seek experiences related to survival and reproduction, such as food and sex. Along the same line, the brain is configured to avoid harmful situations. The circuits in the brain that regulate positive and negative experiences may also be activated by disease. This mechanism is also present in the brains of other mammals such as mice.

A recent study led by David Engblom at Linköping University has discovered a mechanism that explains why diseases lead to depression in the brain. In the study, the researchers focused on the melanocortin 4 receptor which is found on certain nerve cells. The study looked at mice that lacked melanocortin 4 receptors and examined how the animals reacted to disease.

One of the key features of the brain reward system is dopamine, which acts as a chemical messenger between nerve cells. Dopamine improves motivation and causes the brain to strive for rewarding experiences. When the study examined the dopamine mechanism, in the brain, they observed that the dopamine in healthy mice fell in the reward center of the brain when it experienced something unpleasant. In contrast, it increased slightly in the mice that lacked melanocortin 4 receptors.

“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,” says David Engblom.

While we are not sure if the mechanism acts the same way in humans, it is likely to be similar to that shown in the mice. This means that it may be interesting to study the melanocortin 4 receptor in more depth, since it seems to be involved in the dopamine reward mechanism in humans

The article: ”Motivational valence is determined by striatal melanocortin 4 receptors”, Anna Mathia Klawonn, Michael Fritz, Anna Nilsson, Jordi Bonaventura, Kiseko Shionoya, Elahe Mirrasekhian, Urban Karlsson, Maarit Jaarola, Björn Granseth, Anders Blomqvist, Michael Michaelides and David Engblom, J Clin Invest, published online on 18 June 2018, doi: 10.1172/JCI97854