Researchers find common anesthetic can improve social symptoms of depression

LOS ANGELES: Well-being is crucial for everyone, especially when we are lonely or alone.

Depression

is a major issue for many individuals, and finding an effective treatment is critical.
In a recent study published in Molecular Psychiatry, researchers used a

mouse model

of depression to show that one type of

ketamine

(a common anaesthetic) in low doses can improve

social impairments

by restoring function in a specific brain region known as the

anterior insular cortex

.

Ketamine is often used at low doses to treat depression, but its actions in the brain remain relatively unclear. Generally, ketamine refers to a mix of two different forms of ketamine: (S)-ketamine and (R)-ketamine. These two molecules are mirror isomers or enantiomers--they have the same molecular formula, but their three-dimensional forms are mirror images of one another.
Although they usually occur as (S) and (R) pairs, they can also be separated into either (S)-ketamine or (R)-ketamine. Each is beneficial in treating depression, although their specific effects vary.

When the research team decided to test the effects of (S)-ketamine and (R)-ketamine on depression-like symptoms in mice, they first had to decide on an appropriate model. Given that depression and social impairments can be induced by long-term social isolation, they chose a chronic (at least 6 weeks) social isolation mouse model.
The researchers then used a method that allowed them to directly compare neuronal activation throughout the entire brains of mice treated with (S)-ketamine, (R)-ketamine, or saline (as a control) directly after behavioural tests.

"In this way, we were able to observe differences between (S)-ketamine and (R)-ketamine treatments in terms of neuronal activation across the whole brain, without having a predefined hypothesis," said lead author of the study Rei Yokoyama.
"Notably, we found that chronic social isolation led to decreased neuronal activation in the anterior insular cortex--a brain region that is important for emotional regulation--during social contact, and that (R)-ketamine, but not (S)-ketamine, reversed this effect."
The researchers also found that mice treated with (R)-ketamine were better at recognizing unfamiliar versus familiar mice in a social memory test, indicating improved social cognition. Moreover, when neuronal activity was suppressed in the anterior insular cortex, the (R)-ketamine-induced improvements disappeared.
"These findings highlight the importance of the anterior insular cortex for the positive effects of (R)-ketamine on social impairments, at least in mice," said Hitoshi Hashimoto, senior author of the study.
"Together, our results indicate that (R)-ketamine may be better than (S)-ketamine for improving social cognition, and they suggest that this effect is dependent on restoring neuronal activation in the anterior insular cortex."