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Mol Psychiatry ; 29(5): 1406-1416, 2024 May.
Article in English | MEDLINE | ID: mdl-38388704

ABSTRACT

Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. While subanesthetic ketamine is considered effective for cognitive impairments in patients with depression, the neural mechanisms underlying its effects are not well understood. Here we identified unique activation of the anterior insular cortex (aIC) as a characteristic feature in brain-wide regions of mice reared in social isolation and treated with (R)-ketamine, a ketamine enantiomer. Using fiber photometry recording on freely moving mice, we found that social isolation attenuates aIC neuronal activation upon social contact and that (R)-ketamine, but not (S)-ketamine, is able to counteracts this reduction. (R)-ketamine facilitated social cognition in social isolation-reared mice during the social memory test. aIC inactivation offset the effect of (R)-ketamine on social memory. Our results suggest that (R)-ketamine has promising potential as an effective intervention for social cognitive deficits by restoring aIC function.


Subject(s)
Cognitive Dysfunction , Insular Cortex , Ketamine , Social Isolation , Animals , Ketamine/pharmacology , Mice , Male , Insular Cortex/drug effects , Cognitive Dysfunction/drug therapy , Mice, Inbred C57BL , Memory/drug effects , Cognition/drug effects , Social Behavior , Cerebral Cortex/drug effects , Neurons/drug effects , Cognition Disorders/drug therapy
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