Surprise role for dopamine in social interplay

Dopamine is recognised as a messenger molecule in the brain, and is known to play a role in memory, learning, and associated disorders such as addiction. It also helps to control our movements. People with Parkinson's disease develop reduced mobility because their dopamine levels decrease. Previous studies have hinted that it's involved in social behaviour, but little is known about this aspect of its character.

Researchers know it's released by nerve cells called dopamine neurons, and that there are many different groups of these in the brain. The study published in Cell explores a group found in a particular area of the brain called the dorsal raphe nucleus.

"We knew very little about this group of neurons. Now we've shown that they have a fascinating and surprising role in responding to social isolation," said Mark Ungless who leads the Neurophysiology group at the MRC Clinical Sciences Centre based at Imperial College London, and who was the co-senior author of the paper. The study was an international collaboration between Ungless and Kay Tye's lab at the Massachusetts Institute of Technology.

The researchers used optogenetics to show that when this group of dopamine neurons is activated in mice this prompts the animal to interact with others. The finding could hold important clues about how isolation affects people. "Social interactions are no doubt important for our mental health and play a role in conditions such as schizophrenia and depression. Interestingly, these disorders are also associated with dysfunction of dopamine neurons," said Ungless. "We're less likely to be able to help with such conditions if we continue to assume that all dopamine neurons do the same thing."

In the past, dopamine neurons have been thought to respond to positive stimuli, or rewards, such as food. In a previous study, Ungless showed that some are in fact activated in response to negative stimuli, such as pain. He says different groups of dopamine neurons appear to do different things, and that it's increasingly clear that understanding the diversity of these neurons will be key to understanding the many disorders in which they're involved.

When the team stimulated this group of dopamine neurons in the dorsal raphe of mice, they found that these animals spent more time interacting with others. When they inhibited the neurons, the mice interacted less than usual. The suggestion is that when an animal is on its own, these neurons are sensitised, or primed, which indicates to the animal that it's alone -- and encourages it to seek out social interaction.

To explore this further, the researchers activated the neurons only when the mice were in a particular room. They saw that the mice learned to avoid this room, which could suggest either that activating the neurons induces a negative signal, or that the mice have learned to positively seek a room where there's company over a room they know to be empty.

Intriguingly, mice that were kept on their own overnight, and in which the dopamine neurons became particularly active, showed no recognised signs of anxiety. This suggests the dopamine signal is not necessarily negative.

The team also found that the extent to which each mouse altered its behaviour was linked to its social rank. Dominant mice, which had experienced more social exposure, were more sensitive than those lower in the social ranks.

"Social interactions may be more rewarding in dominant males because they have priority access to food and mates, and tend to win territorial conflicts," Tye explained. "As a result, dominant mice may experience a more pronounced loneliness-like state, increasing their drive to seek out social company after periods of isolation."

"These findings provide a launch pad for understanding the biological basis of the experience of social isolation," Tye says. "This could be useful in determining novel targets for social anxiety or autism spectrum disorders. We want to explore ways that this population of neurons might be selectively targeted in hopes of developing a potential new therapy for social impairments."