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Perinatal MAO Inhibition Produces Long-Lasting Impairment of Serotonin Function in Offspring

1
Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059, USA
2
Departments of Biology, McGill University, Montréal, QC H3A 1A1, Canada
3
Department of Psychiatry, Dalhousie University, Halifax, NS B3J 3T4, Canada
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Department of Psychiatry, McGill University, Montréal, QC H3A 1A1, Canada
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Human Genetics, McGill University, Montréal, QC H3A 1A1, Canada
*
Author to whom correspondence should be addressed.
Deceased.
Brain Sci. 2018, 8(6), 106; https://doi.org/10.3390/brainsci8060106
Received: 18 May 2018 / Revised: 7 June 2018 / Accepted: 9 June 2018 / Published: 11 June 2018
In addition to transmitter functions, many neuroamines have trophic or ontogenetic regulatory effects important to both normal and disordered brain development. In previous work (Mejia et al., 2002), we showed that pharmacologically inhibiting monoamine oxidase (MAO) activity during murine gestation increases the prevalence of behaviors thought to reflect impulsivity and aggression. The goal of the present study was to determine the extent to which this treatment influences dopamine and serotonin innervation of murine cortical and subcortical areas, as measured by regional density of dopamine (DAT) and serotonin transporters (SERT). We measured DAT and SERT densities at 3 developmental times (PND 14, 35 and 90) following inhibition of MAO A, or MAO B or both throughout murine gestation and early post-natal development. DAT binding was unaltered within the nigrostriatal pathway, but concurrent inhibition of MAO-A and MAO-B significantly and specifically reduced SERT binding by 10–25% in both the frontal cortex and raphe nuclei. Low levels of SERT binding persisted (PND 35, 90) after the termination (PND 21) of exposure to MAO inhibitors and was most marked in brain structures germane to the previously described behavioral changes. The relatively modest level of enzyme inhibition (25–40%) required to produce these effects mandates care in the use of any compound which might inhibit MAO activity during gestation. View Full-Text
Keywords: serotonin transporter; dopamine transporter; neurodevelopment; MAO inhibition; aggression; anxiety serotonin transporter; dopamine transporter; neurodevelopment; MAO inhibition; aggression; anxiety
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Burke, M.W.; Fillion, M.; Mejia, J.; Ervin, F.R.; Palmour, R.M. Perinatal MAO Inhibition Produces Long-Lasting Impairment of Serotonin Function in Offspring. Brain Sci. 2018, 8, 106.

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