Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. This study found that (R)-ketamine, a ketamine enantiomer, uniquely activates the anterior insular cortex (aIC) in socially isolated mice. Fiber photometry revealed that social isolation attenuates aIC neuronal activation during social contact, an effect reversed by (R)-ketamine but not (S)-ketamine. (R)-ketamine also improved social cognition in these mice, an effect blocked by aIC inactivation. These results suggest (R)-ketamine's potential as an effective intervention for social cognitive deficits by restoring aIC function.
