Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase.

Abstract:

:Genetically engineered mice with targeted disruption of the neuronal nitric oxide synthase (nNOS) gene established the inhibitory role of nitric oxide (NO) in male impulsive aggressive behavior. This was later confirmed by using selective nNOS inhibitors in male wild-type mice. The molecular mechanisms accounting for the aggressive behavior caused by the lack of neuronally derived NO is not known. Recent studies suggest that central serotonergic neuronal circuits and particularly 5-HT(1A) and 5-HT(1B) receptors play a prominent role in the regulation of aggression. Accordingly, we investigated whether the aggressiveness caused by the lack of nNOS might be because of alterations in serotonergic function. We now demonstrate that the excessive aggressiveness and impulsiveness of nNOS knockout mice is caused by selective decrements in serotonin (5-HT) turnover and deficient 5-HT(1A) and 5-HT(1B) receptor function in brain regions regulating emotion. These results indicate an important role for NO in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressiveness and impulsivity.

authors

Chiavegatto S,Dawson VL,Mamounas LA,Koliatsos VE,Dawson TM,Nelson RJ

doi

10.1073/pnas.031487198

keywords:

subject

Has Abstract

pub_date

2001-01-30 00:00:00

pages

1277-81

issue

3

eissn

0027-8424

issn

1091-6490

pii

031487198

journal_volume

98

pub_type

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