Intranasal Administration of Oxytocin Attenuates Social Recognition Deficits and Increases Prefrontal Cortex Inhibitory Postsynaptic Currents following Traumatic Brain Injury

eNeuro. 2021 Jun 11;8(3):ENEURO.0061-21.2021. doi: 10.1523/ENEURO.0061-21.2021. Print 2021 May-Jun.

Abstract

Pediatric traumatic brain injury (TBI) results in heightened risk for social deficits that can emerge during adolescence and adulthood. A moderate TBI in male and female rats on postnatal day 11 (equivalent to children below the age of 4) resulted in impairments in social novelty recognition, defined as the preference for interacting with a novel rat compared with a familiar rat, but not sociability, defined as the preference for interacting with a rat compared with an object in the three-chamber test when tested at four weeks (adolescence) and eight weeks (adulthood) postinjury. The deficits in social recognition were not accompanied by deficits in novel object recognition memory and were associated with a decrease in the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from pyramidal neurons within Layer II/III of the medial prefrontal cortex (mPFC). Whereas TBI did not affect the expression of oxytocin (OXT) or the OXT receptor (OXTR) mRNAs in the hypothalamus and mPFC, respectively, intranasal administration of OXT before behavioral testing was found to reduce impairments in social novelty recognition and increase IPSC frequency in the mPFC in brain-injured animals. These results suggest that TBI-induced deficits in social behavior may be linked to increased excitability of neurons in the mPFC and suggests that the regulation of GABAergic neurotransmission in this region as a potential mechanism underlying these deficits.

Keywords: GABAergic neurotransmission; excitability; intranasal administration; oxytocin; pediatric TBI; social behavior.

MeSH terms

  • Administration, Intranasal
  • Adult
  • Animals
  • Brain Injuries, Traumatic* / drug therapy
  • Child
  • Female
  • Humans
  • Inhibitory Postsynaptic Potentials
  • Male
  • Oxytocin*
  • Prefrontal Cortex
  • Rats
  • Social Behavior

Substances

  • Oxytocin