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Home » (R)-ketamine improves social impairments in mice by restoring brain region activity

(R)-ketamine improves social impairments in mice by restoring brain region activity

In a groundbreaking study featured in Molecular Psychiatry, a team of researchers hailing from Osaka University has utilized a of to uncover a fascinating revelation: a specific form of , administered in low doses, can ameliorate social impairments by rejuvenating functionality within the anterior insular cortex, a key brain region implicated in emotional regulation.

Ketamine, a widely used anesthetic, is increasingly recognized for its therapeutic potential in treating depression, yet its precise mechanisms of action in the brain remain enigmatic. Typically, ketamine encompasses two distinct forms: and , which are mirror isomers—possessing identical molecular formulas but differing in three-dimensional structure. While both (S)-ketamine and (R)-ketamine exhibit antidepressant properties, their nuanced effects diverge.

When the researchers embarked on investigating the impacts of (S)-ketamine versus (R)-ketamine on depression-like symptoms in , they embarked on the quest for a suitable model. Opting for a chronic social isolation mouse model—a paradigm known to induce depression and social impairments over extended periods (at least 6 weeks)—the researchers delved into their experimental endeavors.

Employing a methodology enabling direct comparison of neuronal activation patterns across the entire brains of mice subjected to (S)-ketamine, (R)-ketamine, or saline (as a control) post-behavioral assessments, the team aimed to discern differential effects without predetermined biases.

Lead author Rei Yokoyama elucidates, “This approach facilitated unbiased observation of neuronal activation discrepancies between (S)-ketamine and (R)-ketamine treatments, revealing intriguing insights. Notably, we identified diminished neuronal activation within the anterior insular cortex—a pivotal hub for emotional regulation—among socially isolated mice, a deficit rectified by (R)-ketamine, but not (S)-ketamine.”

Moreover, (R)-ketamine-treated mice exhibited heightened proficiency in discriminating unfamiliar versus familiar peers in a social memory assessment, indicative of enhanced . Intriguingly, suppression of neuronal activity within the anterior insular cortex abrogated the benefits conferred by (R)-ketamine.

Senior author Hitoshi Hashimoto underscores, “These findings underscore the centrality of the anterior insular cortex in mediating the beneficial effects of (R)-ketamine on social impairments in mice. Our results suggest the superiority of (R)-ketamine in enhancing social cognition, contingent upon restoration of neuronal activation within the anterior insular cortex.”

Against the backdrop of escalating rates of social isolation and depression globally, these revelations bear immense significance. (R)-ketamine emerges as a promising intervention for alleviating isolation-induced social deficits, potentially augmenting the quality of life for individuals grappling with associated afflictions.

Source: Osaka University

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