Aggressive behavior in male mice lacking the gene for neuronal nitric oxide synthase requires testosterone

Lance J. Kriegsfeld, Ted M. Dawson, Valina L. Dawson, Randy J. Nelson, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Nitric oxide acts as a neural messenger in both the central and peripheral nervous systems. Mice with targeted disruption of the neuronal isoform of nitric oxide synthase (nNOS - / -) are extremely aggressive relative to wild-type (WT) mice. Male nNOS - / - mice exhibit an increase in the number and duration of aggressive encounters compared to WT animals when tested in a variety of paradigms used to test rodent aggression. This inappropriate aggressive behavior has only been observed in male nNOS - / - mice; nNOS - / - females, like female WT mice, exhibit little or no aggression. The present study sought to test the dependence of increased aggressive behavior in nNOS - / - males on testosterone. Intact nNOS - / - males exhibited elevated levels of aggression relative to intact WT males. Castration reduced aggression in both WT and nNOS - / - males to equivalent low levels. Testosterone replacement restored aggression to precastration levels in both genotypes. These data provide evidence that increased aggressive behavior of nNOS - / - mice, like aggression in WT mice, is testosterone-dependent.

Original languageEnglish (US)
Pages (from-to)66-70
Number of pages5
JournalBrain research
Issue number1
StatePublished - Sep 19 1997


  • Agonistic behavior
  • Androgen
  • Behavioral neuroendocrinology
  • Gonadectomy
  • Knockout
  • Sex steroid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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