Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model

Kayla R. Nygaard, Raylynn G. Swift, Rebecca M. Glick, Rachael E. Wagner, Susan Maloney, Georgianna G. Gould, Joseph D. Dougherty

Research output: Contribution to journalArticlepeer-review

Abstract

Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation is hypothesized to be involved as some studies have shown elevated blood OT and altered OT receptor expression in patients. A “Complete Deletion” (CD) mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These CD mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether OT dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an OT receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in CD mice. Thus, increased OT signaling is not acutely responsible for this phenotype. We also evaluated OT receptor and serotonin transporter availability in regions related to fear learning, memory and sociability using autoradiography in wild type and CD mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in OT receptor expression in the lateral septal nucleus and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.

Original languageEnglish
JournalGenes, Brain and Behavior
DOIs
StateAccepted/In press - 2021

Keywords

  • associative fear
  • autoradiography
  • behavioral genetics
  • conditioned fear
  • mouse model
  • OXTR
  • oxytocin
  • oxytocin receptor antagonist
  • SERT
  • Williams Syndrome

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