NMDARs Mediate the Role of Monoamine Oxidase A in Pathological Aggression
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Issue Date
2012-06-20Author
Bortolato, Marco
Godar, Sean C.
Melis, Miriam
Soggiu, Alessio
Roncada, Paola
Casu, Angelo
Flore, Giovanna
Chen, Kevin
Frau, Roberto
Urbani, Andrea
Castelli, M. Paola
Devoto, Paola
Shih, Jean C.
Publisher
Society for Neuroscience
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
Converging evidence shows that monoamine oxidase A (MAO A), the key enzyme catalyzing serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE) degradation, is a primary factor in the pathophysiology of antisocial and aggressive behavior. Accordingly, male MAO A-deficient humans and mice exhibit an extreme predisposition to aggressive outbursts in response to stress. As NMDARs regulate the emotional reactivity to social and environmental stimuli, we hypothesized their involvement in the modulation of aggression mediated by MAO A. In comparison with WT male mice, MAO A KO counterparts exhibited increases in 5-HT and NE levels across all brain regions, but no difference in glutamate concentrations and NMDAR binding. Notably, the prefrontal cortex (PFC) of MAO A KO mice exhibited higher expression of NR2A and NR2B, as well as lower levels of glycosylated NR1 subunits. In line with these changes, the current amplitude and decay time of NMDARs in PFC was significantly reduced. Furthermore, the currents of these receptors were hypersensitive to the action of the antagonists of the NMDAR complex (dizocilpine), as well as NR2A (PEAQX) and NR2B (Ro 25-6981) subunits. Notably, systemic administration of these agents selectively countered the enhanced aggression in MAO A KO mice, at doses that did not inherently affect motor activity. Our findings suggest that the role of MAO A in pathological aggression may be mediated by changes in NMDAR subunit composition in the PFC, and point to a critical function of this receptor in the molecular bases of antisocial personality.
Description
This is the publisher's version, also available electronically from http://www.jneurosci.org/content/32/25/8574
ISSN
0270-6474Collections
- Pharmacy Scholarly Works [293]
Citation
Bortolato, Marco et al. (2011). NMDARs mediate the role of monoamine oxidase A in pathological aggression. The Journal of Neuroscience 32(25):8574-8582. http://www.dx.doi.org/10.1523/JNEUROSCI.0225-12.2012
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