Abstract
Background
The neuropeptide oxytocin (OT) is a key regulator of social and emotional behaviors.
The effects of OT are context dependent, and it has been proposed that OT increases
the salience of both positive and negative social cues. Here we tested whether the
bed nucleus of the stria terminalis (BNST) mediates anxiogenic effects of OT.
Methods
First, we studied the effects of systemic administration of an OT receptor (OTR) antagonist
L-368,899 on social behavior in male and female California mice exposed to social
defeat. We examined the effect of L-368,899 on G protein activation and used early
growth response factor 1 immunohistochemistry to identify potential sites of OTR action.
Finally, we examined the effects of L-368,899 infused in the BNST on behavior.
Results
A single dose of systemic L-368,899 increased social approach in stressed female mice
and decreased social approach in male mice naïve to defeat. L-368,899 prevented OT
activation of G proteins and did not activate G proteins in the absence of OT. Intranasal
OT, which reduces social approach in female mice but not male mice, increased early
growth response factor 1 immunoreactivity in the nucleus accumbens core and anteromedial
BNST in female mice but not in male mice. Stressed female mice that received an infusion
of L-368,899 into the anteromedial BNST but not the nucleus accumbens core increased
social approach and decreased social vigilance responses.
Conclusions
Our results suggest that OTR activation in anteromedial BNST induces a vigilance response
in which individuals avoid, yet attend to, unfamiliar social contexts. Our results
suggest that OTR antagonists may have unappreciated therapeutic potential for stress-induced
psychiatric disorders.
Keywords
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Article info
Publication history
Published online: September 13, 2017
Accepted:
August 29,
2017
Received in revised form:
August 16,
2017
Received:
June 7,
2017
Identification
Copyright
© 2017 Society of Biological Psychiatry.
