The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake
dc.contributor.author | Godar, Sean C. | |
dc.contributor.author | Bortolato, Marco | |
dc.contributor.author | Castelli, M. Paola | |
dc.contributor.author | Casti, Alberto | |
dc.contributor.author | Casu, Angelo | |
dc.contributor.author | Chen, Kevin | |
dc.contributor.author | Ennas, M. Grazia | |
dc.contributor.author | Tambaro, Simone | |
dc.contributor.author | Shih, Jean C. | |
dc.date.accessioned | 2017-06-16T18:36:06Z | |
dc.date.available | 2017-06-16T18:36:06Z | |
dc.date.issued | 2014-09 | |
dc.identifier.citation | Godar, S. C., Bortolato, M., Castelli, M. P., Casti, A., Casu, A., Chen, K., … Shih, J. C. (2014). The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake. Journal of Psychiatric Research, 56, 1–9. http://doi.org/10.1016/j.jpsychires.2014.04.014 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24519 | |
dc.description.abstract | The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-ANeo mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-ANeo mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Serotonin | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Serotonin transporter | en_US |
dc.subject | Animal models | en_US |
dc.title | The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Godar, Sean C. | |
kusw.kuauthor | Bortolato, Marco | |
kusw.kuauthor | Shih, Jean C. | |
kusw.kudepartment | Pharmacy | en_US |
dc.identifier.doi | 10.1016/j.jpsychires.2014.04.014 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4114985 | en_US |
dc.rights.accessrights | openAccess |
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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 4.0 (CC BY-NC-ND 4.0), 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.