Aggressive behavior in male mice lacking the gene for neuronal nitric oxide synthase requires testosterone.
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.
Kriegsfeld
L J
LJ
Department of Psychology, The Johns Hopkins University, Baltimore, MD 21205, USA. lance@ren.psy.jhu.edu
Dawson
T M
TM
Dawson
V L
VL
Nelson
R J
RJ
Snyder
S H
SH
D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D009919:Orchiectomy; D012016:Reference Values; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*
D013739:Testosterone; D019001:Nitric Oxide Synthase