Acute and Repeated Intranasal Oxytocin Differentially Modulate Brain-wide Functional Connectivity

Area of Science:

• Neuroscience
• Neuroendocrinology
• Systems Neuroscience

Background:

• Central oxytocin (OXT) influences socio-affective behaviors.
• Intranasal OXT is explored for social deficits in conditions like autism spectrum disorders (ASD).
• Neural circuitry and network effects of OXT remain unclear, especially with long-term use.

Purpose of the Study:

• To map brain-wide functional networks affected by acute and repeated intranasal OXT administration in mice.
• To investigate the neuroadaptive cascade triggered by long-term OXT dosing at the network level.

Main Methods:

• fMRI-based circuit mapping in adult mice.
• Acute and seven-day repeated intranasal OXT dosing.
• Cerebral blood volume (CBV) mapping to assess fMRI activity.

Main Results:

• Acute and chronic OXT showed comparable fMRI activity but distinct functional connectivity patterns.
• Acute OXT enhanced limbic connectivity; repeated OXT increased widespread connectivity, notably coupling the amygdala with cortical areas.
• Repeated OXT administration paradoxically reduced social interaction and communication in wild-type mice.

Conclusions:

• Exogenous OXT engages specific network substrates.
• Repeated OXT significantly reconfigures brain-wide connectivity, creating aberrant cortico-limbic coupling.
• Divergent network effects may explain varied clinical outcomes of acute versus chronic OXT use.