The relation of developmental changes in brain serotonin transporter (5HTT) and 5HT1A receptor binding to emotional behavior in female rhesus monkeys: effects of social status and 5HTT genotype

• Type of Material: Article
• Authors: Molly Embree, Emory University; Vasiliki J. Michopoulos, Emory University; John R Votaw, Emory University; Ronald Voll, Emory University; Jiyoung Mun, Emory University; Jeffrey Scott Stehouwer, Emory University; Mark Goodman, Emory University; Mark Wilson, Emory University; Mar Sanchez, Emory University
• Language: English
• Date: 2013-01-03
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuroscience.2012.10.016
• Title of Journal or Parent Work: Neuroscience
• ISSN: 0306-4522
• Volume: 228
• Start Page: 83
• End Page: 100
• Grant/Funding Information: The project described was supported by Grant Numbers MH079100, F31 MH086203 (BRH) and F31 MH085445 (VM) from the National Institute of Mental Health (NIMH).; The project was also funded by the National Center for Research Resources P51RR165 (YNPRC Base grant) and is currently supported by the Office of Research Infrastructure Programs/OD P51OD11132.
• Keywords: serotonin transporter polymorphisms; nonhuman primates; [18F]FEmZIENT; social stress; p-[18F]MPPF
• Research Categories: Biology, Neuroscience

Abstract

The goal of the present study was to examine how social subordination stress and 5HTT polymorphisms affect the development of brain serotonin (5HT) systems during the pubertal transition in female rhesus monkeys. We also examined associations with developmental changes in emotional reactivity in response to a standardized behavioral test, the Human Intruder (HI). Our findings provide the first longitudinal evidence of developmental increases in 5HT1A receptor and 5HTT binding in the brain of female primates from pre- to peripuberty. The increase in 5HT1A BPND in these socially housed female rhesus monkeys is a robust finding, occurring across all groups, regardless of social status or 5HTT genotype, and occurring in left and right hemispheres of all prefrontal regions studied, as well as amygdala, hippocampus, hypothalamus, and raphe nuclei. 5HTT BPND also showed an increase with age in raphe, anterior cingulate cortex, and dorsolateral prefrontal cortex. These changes in brain 5HT systems take place as females establish more adult-like patterns of social behavior, as well as during the HI paradigm. Indeed, the main developmental changes in behavior during the HI (increase in freezing and decrease in submission/appeasement) were related to neurodevelopmental increases in 5HT1A receptors and 5HTT, because the associations between these behaviors and 5HT endpoints emerge at peripuberty. We detected an effect of social status on 5HT1A BPND in the hypothalamus and on 5HTT BPND in the orbitofrontal cortex, with subordinates showing higher BPND than dominants in both cases during the pubertal transition. No main effects of 5HTT genotype were observed for 5HT1A or 5HTT BPND. Our findings indicate that adolescence in female rhesus monkeys is a period of central 5HT reorganization, partly influenced by exposure to the social stress of subordination, that likely functions to integrate adrenal and gonadal systems and shape the behavioral response to emotionally challenging social situations.