Study Finds Low Doses of Common Anesthetic Improve Depression Symptoms

Everyone should prioritize their well-being, especially when they are isolated or alone. For many people, depression is a serious issue, so finding a good therapist is essential. Low doses of ketamine, a common anesthetic, can restore social deficits by restoring function in the anterior insular cortex, according to a study published in Molecular Psychiatry. Although ketamine is frequently used in small doses to treat depression, little is known about how it works in the brain. In general, the term “ketamine” describes a combination of the two distinct ketamine forms, (S)-ketamine and (R)-ketamine.

Despite having the same chemical formula, these two molecules are mirror isomers, or enantiomers, of one another in three dimensions. Despite the fact that they are typically found in pairs, they can also be divided into (S)- and (R)-ketamine. All are helpful in the treatment of depression, though their precise effects differ. The research team had to choose a suitable model before deciding to examine the effects of (S)- and (R)-ketamine on mice’s depression-like symptoms.

They selected a chronic (at least 6 weeks) social isolation mouse model because prolonged social isolation can cause depression and social impairments. Then, following behavioral tests, the researchers employed a technique that enabled them to compare neuronal activation throughout the entire brains of mice treated with (S)-ketamine, (R)-ketamine, or saline (as a control).

“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.”