Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA

TLDR

MAOA deficiency, which impairs serotonin and norepinephrine degradation, has been linked to aggressive behavior in a Dutch family. A transgenic mouse line was created with a deletion of the MAOA gene, providing an animal model of MAOA deficiency. MAOA‑deficient mice exhibit markedly elevated serotonin and norepinephrine levels, cytoarchitectural changes in the somatosensory cortex, behavioral abnormalities in pups that are reversible with a serotonin synthesis inhibitor, and increased aggression in adult males.

Abstract

Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males.