How to improve the social status of an anxious rat

by Tim Newman (Medical News Today, Saturday 5 Dec 2015)

A groundbreaking study has identified a brain region in rats that, when stimulated by vitamin B3, makes them less anxious and more socially successful.

It goes without saying that individuals within a society (rats or humans) have differing levels of confidence and anxiety.

Some view all new situations as potentially threatening, whereas others might find them exciting or stimulating.

The role that anxiety plays in the shuffling of society has long been questioned by sociologists, psychologists and neuroscientists alike. Recent research adds some intriguing brain chemistry into the mix.

Societies of rats and humans are, obviously, impressively complex. Your ability to thrive, even in the rat world, is dependent on numerous factors, including age, size and previous social experience. Anxiety levels, as we shall see, are also implicated.

In rats, it is the least anxious members of a group that climb the auspicious social ladder. Rats with a more anxious bent rarely achieve top social statuses. Additionally, a rat’s well-being is negatively impacted by a low social standing

Anxious rats (with some parallels to humans) can enter a negative cycle of so-called social subordination. An individual that cannot compete socially because of their anxiety will only be made to feel more anxious by their repeated failures on that slippery rat ladder.

Anxious rats
The current investigation was carried out by Carmen Sandi and her team at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. Sandi’s team, investigating the biological basis of social competition and anxiety, aimed to flesh out the links between social success and anxiety.

The team started their investigation by ranking the rats by their degree of anxiety traits. They next pitted high-anxiety rats against low-anxiety rats. As expected, high-anxiety rats automatically took on the roles of lower status animals, and vice versa.

Anxiety levels seemed to play a key role in the way that the animals behaved around each other. They naturally fell into social strata according to their confidence level.

The team at EPFL also measured any biological changes in the animals’ brains. They found some interesting differences in an area known as the nucleus accumbens.

The highly anxious individuals showed a marked decrease in the activity of the mitochondria in their nucleus accumbens. Mitochondria, the powerhouses of the cell, were observed to produce less ATP (a molecule that transports energy for the cells to use).

The role of the nucleus accumbens
The nucleus accumbens is an area of the brain believed to be important in mediating behaviors including reward and satisfaction.

The region is also thought to play a role in obsessive-compulsive disorder, anxiety disorders, Tourette’s syndrome, Parkinson’s disease, depression, bipolar disorder, Alzheimer’s disease, Huntington’s disease, obesity and drug abuse.

This ever-growing list of disorders has prompted plenty of research.

Reversing the anxiety
The next question Sandi wanted to answer was: what happens if activity in the nucleus accumbens is reversed?

The team put the question to the test. They delivered drugs to the nucleus accumbens that either enhanced or diminished activity within the mitochondria of the nucleus accumbens.

When rats received the blocking agents, they became more anxious, and their social competitiveness diminished. Conversely, when they were given enhancers, including the vitamin B3, the rats were found to increase in confidence and their social prowess improved in line.

Once the blocking or enhancing agents had worn off, the rats returned to their pre-drug levels of both anxiety and social standing.

Published in Proceedings of the National Academy of Sciences, the results can only be applied to rats, but the implications are thoroughly intriguing. It is difficult not to draw comparisons to humanity, but we must fight the urge at this early stage.

Sandi says:

“Social interactions are immensely complex, they involve so many factors that it is difficult to examine the impact of each in isolation.

However, this is an exciting finding; it shows a brain mechanism whereby anxious personality affects social competitiveness of individuals, and it points to very promising directions in this field.”

Future research will investigate whether mitochondrial function in the nucleus accumbens might be used as a molecular marker for mood disorders in humans. There is also the potential of targeting the nucleus accumbens for pharmaceutical interventions in the treatment of the conditions mentioned above.