Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice
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Issue Date
2013-12Author
Bortolato, Marco
Godar, Sean C.
Tambaro, Simone
Li, Felix G.
Devoto, Paola
Coba, Marcelo P.
Chen, Kevin
Shih, Jean C.
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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Show full item recordAbstract
Monoamine oxidase (MAO) A, the major enzyme catalyzing the oxidative degradation of serotonin (5-hydroxytryptamine, 5-HT), plays a key role in emotional regulation. In humans and mice, MAO-A deficiency results in high 5-HT levels, antisocial, aggressive, and perseverative behaviors. We previously showed that the elevation in brain 5-HT levels in MAO-A knockout (KO) mice is particularly marked during the first two weeks of postnatal life. Building on this finding, we hypothesized that the reduction of 5-HT levels during these early stages may lead to enduring attenuations of the aggression and other behavioral aberrances observed in MAO-A KO mice. To test this possibility, MAO-A KO mice were treated with daily injections of a 5-HT synthesis blocker, the tryptophan hydroxylase inhibitor p-chloro-phenylalanine (pCPA, 300 mg/kg/day, IP), from postnatal day 1 through 7. As expected, this regimen significantly reduced 5-HT forebrain levels in MAO-A KO pups. These neurochemical changes persisted throughout adulthood, and resulted in significant reductions in marble-burying behavior, as well as increases in spontaneous alternations within a T-maze. Conversely, pCPA-treated MAO-A KO mice did not exhibit significant changes in anxiety-like behaviors in a novel open-field and elevated plus-maze; furthermore, this regimen did not modify their social deficits, aggressive behaviors and impairments in tactile sensitivity. Treatment with pCPA from postnatal day 8 through 14 elicited similar, yet milder, behavioral effects on marble-burying behavior. These results suggest that early developmental enhancements in 5-HT levels have long-term effects on the modulation of behavioral flexibility associated with MAO-A deficiency.
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Citation
Bortolato, M., Godar, S. C., Tambaro, S., Li, F. G., Devoto, P., Coba, M. P., … Shih, J. C. (2013). Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice. Neuropharmacology, 0, 10.1016/j.neuropharm.2013.07.003. http://doi.org/10.1016/j.neuropharm.2013.07.003
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.