The Journal of Neuroscience, 1999, 19:RC30:1-5
RAPID COMMUNICATION
Elimination of Aggressive Behavior in Male Mice Lacking
Endothelial Nitric Oxide Synthase
Gregory E.
Demas1, 6,
Lance J.
Kriegsfeld1,
Seth
Blackshaw2,
Paul
Huang5,
Stephen C.
Gammie1,
Randy J.
Nelson1, 2, and
Solomon H.
Snyder2, 3, 4
Department of 1 Psychology, Johns Hopkins University,
and Departments of 2 Neuroscience,
3 Pharmacology and Molecular Sciences, and
4 Psychiatry, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21218, 5 Massachusetts General
Hospital, Division of Cardiology, Boston, Massachusetts 02114, and
6 Georgia State University, Departments of Psychology and
Biology, Atlanta, Georgia 30303
Male mice with targeted deletion of the gene encoding the neuronal
isoform of nitric oxide synthase (nNOS
/) display
increased aggressive behavior compared with wild-type (WT) mice.
Specific pharmacological inhibition of nNOS with 7-nitroindazole also
augments aggressive behavior. We report here that male mice with
targeted deletion of the gene encoding endothelial NOS
(eNOS/) display dramatic reductions in
aggression. The effects are selective, because an extensive battery of
behavioral tests reveals no other deficits. In the resident-intruder
model of aggression, resident eNOS/ males show
virtually no aggression. Latency for aggression onset is 25-30 times
longer in eNOS/ males compared with WT males in
the rare instances of aggressive behaviors. Similarly, a striking lack
of aggression is noted in tests of aggression among groups of four mice
monitored in neutral cages. Although eNOS/ mice
are hypertensive (~14 mmHg blood pressure elevation),
hypertension does not appear responsible for the diminished aggression.
Reduction of hypertension with hydralazine does not change the
prevalence of aggression in eNOS/ mice.
Extensive examination of brains from eNOS/ male
mice reveals no obvious neural damage from chronic hypertension. In situ hybridization in WT animals reveals eNOS mRNA in
the brain associated exclusively with blood vessels and no neuronal
localizations. Accordingly, vascular eNOS in the brain appears capable
of influencing behavior with considerable selectivity.
Key words:
aggression; hypertension; 7-nitroindazole; nitroarginine; nitric oxide synthase; endothelium
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