Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing

Behav Brain Res. 2008 Feb 11;187(1):109-15. doi: 10.1016/j.bbr.2007.08.033. Epub 2007 Sep 4.


Many psychological disorders are characterized by anxiety and alterations in social interactions. Recent studies demonstrate that the chemical messenger nitric oxide (NO) can regulate both anxiety and social behaviours. We tested whether an enzyme that produces NO in the brain, neuronal nitric oxide synthase (nNOS), serves as an interface between social interactions and anxiety-like behaviour. Several investigators have observed that mice increase anxiety-like responses in the elevated plus-maze after pair housing. nNOS gene deletion and 3-Bromo-7-Nitroindazole were used to inhibit the production of neuronal NO. Similar to previous studies, pair housing reduced open arm exploration in the elevated plus-maze. Pair housing also increased corticotropin-releasing hormone (CRH) immunoreactive cells in the paraventricular nucleus (PVN) of the hypothalamus. Inhibition of NO production increased open arm exploration in pair-housed mice but decreased open arm exploration in individually housed mice. These results suggest that the effect of nNOS inhibition on anxiety-like responses is context dependent and that behavioural responses to social housing are altered after nNOS inhibition. This research suggests that NO may play an important role in mediating the effect social interactions have on anxiety.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anxiety / psychology*
  • Corticotropin-Releasing Hormone / blood
  • Enzyme Inhibitors / pharmacology*
  • Genotype
  • Housing, Animal
  • Immunohistochemistry
  • Indazoles / pharmacology
  • Mice
  • Mice, Knockout
  • Motor Activity / physiology
  • Nitric Oxide Synthase Type I / antagonists & inhibitors*
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Social Environment*


  • 3-bromo-7-nitroindazole
  • Enzyme Inhibitors
  • Indazoles
  • Corticotropin-Releasing Hormone
  • Nitric Oxide Synthase Type I