Intranasal oxytocin (OXT) administration has shown promise as a putative treatment for disorders characterized by social impairments. However, the brain-wide substrates engaged by this neuropeptide remain elusive. By using mouse fMRI, we show that the circuits engaged by intranasal OXT are differentially affected by the duration of OXT dosing. Specifically, acute OXT administration increases brain connectivity in key nodes of the social brain. By contrast, repeated dosing exacerbates inter-regional coupling and results in paradoxical social impairments in control “wild type” mice. These result have implications for clinical testing of OXT in control and pathological conditions.
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