Research published in Molecular Psychiatry indicates that administering low doses of ketamine, a commonly used anaesthetic, can alleviate social deficits by reinstating functionality in the anterior insular cortex. While ketamine is frequently employed in low doses for depression treatment, its precise mechanisms within the brain remain somewhat ambiguous. Ketamine typically consists of a blend of two distinct forms: (S)-ketamine and (R)-ketamine.
When the research team opted to examine the impacts of (S)-ketamine and (R)-ketamine on depression-like symptoms in mice, they initially needed to select a suitable model. Recognising that prolonged social isolation can induce depression and social impairments, they selected a chronic (lasting at least 6 weeks) social isolation mouse model.
Subsequently, the researchers employed a technique enabling them to directly compare neuronal activation across the entire brains of mice treated with (S)-ketamine, (R)-ketamine, or saline (utilised as a control) immediately following behavioural assessments.
"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 Rei Yokoyama, the study's lead author.
"Notably, we found that chronic social isolation led to decreased neuronal activation in the anterior insular cortex—a brain region important for emotional regulation—during social contact and that (R)-ketamine, but not (S)-ketamine, reversed this effect.”
"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.
