Low doses of ketamine can restore social deficits by restoring function in anterior insular cortex, says study.
Well-being is important for everyone, especially when
we are lonely or alone. Depression is a serious problem for many people, and
finding an effective therapy is crucial.
A study published in Molecular Psychiatry found that
low doses of ketamine, a common anaesthetic, can restore social deficits by
restoring function in 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."
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