Abstract
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.
Highlights
Low levels of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) are thought to be associated with aggression and impulsivity [1,2,3,4,5,6,7,8]
The present findings suggest that the critical level of monoamine oxidase (MAO) inhibition, which subserves serotonin transporters (SERT) reduction, is in
The major finding reported here is that the prenatal inhibition of MAO-A and B significantly and reduced SERT binding by up to 25% in the cortex and raphe nucleus at defined developmental stages, persisting into adulthood
Summary
Low levels of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) are thought to be associated with aggression and impulsivity [1,2,3,4,5,6,7,8]. A striking example of this relationship is a single Dutch kindred [9,10] in which approximately half of the male offspring displayed mild mental retardation and aggressive impulsive behavior linked to a point mutation of the monoamine MAO-A gene [10]. In affected individuals of the Dutch kindred, MAO-A activity was ablated, and levels of serotonin and serotonin metabolites were abnormally high, providing a paradox with respect to the “low serotonin-elevated aggression” model [10,13].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
