Researchers discover the science behind abandonment

What happens when we give up? Inside the brain, a group of cells called nociceptin neurons becomes very active before the point of arrest of a mouse. They emit nociceptin, a complex molecule that suppresses dopamine, a chemical that is largely badociated with motivation.

The results, reported on July 25 in Cell, offers a new insight into the complex world of motivation and reward.

The neurons of nociceptin are located near an area of ​​the brain called the ventral tegmental area. VTA contains neurons that release dopamine during pleasant activities. Although scientists have previously studied the effects of simple and fast neurotransmitters on dopaminergic neurons, this study is among the first to describe the effects of this complex system of modulation of nociception.

"We are taking an entirely new angle on a region of the brain called VTA," said lead co-author Christian Pedersen, a fourth-year doctorate. Bioengineering student at the University of Washington School of Medicine and UW College of Engineering.

Researchers from the UW School of Medicine and the Washington University School of Medicine as well as colleagues from other universities have spent four years studying the role of nociceptin in regulating motivation.

"The big discovery is that the large, complex neurotransmitters called neuropeptides have a very robust effect on animal behavior by acting on the VTA," said Pedersen.

The researchers said this discovery could help people find motivation when they are depressed and conversely decrease motivation to take drugs for addiction-related disorders, such as addiction.

The discovery came by looking at the neurons in mice looking for sucrose. The mice had to push their muzzle into a port to get sucrose. At first, it was easy, then it became two pokes, then five, increasing exponentially, and so on. Finally, all the mice gave up. Records of neuronal activity revealed that these "demotivation" or "frustration" neurons became more active when mice stopped looking for sucrose.

In mammals, the neural circuits that underlie reward seeking are regulated by mechanisms to maintain homeostasis, ie the tendency to maintain internal stability to offset environmental changes. In the wild, animals are less motivated to seek rewards in environments where resources are scarce. Persistence in the search for uncertain rewards can be disadvantageous because of risky exposure to predators or energy expenditure, the researchers noted.

Deficiencies in these regulatory processes in humans can be manifested by behavioral dysfunctions, including depression, addiction, and eating disorders.

Michael Bruchas, Senior Author, Professor of Anesthesiology and Pain Management and Pharmacology at the University of Washington School of Medicine, is one of the leading faculties of the new Center for Neurobiology of Addiction, Pain and emotions of the UW. He said the results could greatly help find help for patients whose motivational neurons are not functioning properly.

"We could think of different scenarios in which people are not motivated, like depression, and block these neurons and receptors to help them feel better," he said. "That's what makes the strength of the discovery of these cells neuropsychiatric diseases that impact motivation could be improved."

As far as the future is concerned, these neurons could perhaps be modified in people who are looking for drugs or who have another addiction.