Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques

Abstract

The moderating effect of early experience on genebehavior associations has been well characterized. The molecular events that allow for such moderation are not well understood, however. We assessed the impact of early experience and serotonin transporter linked promoter polymorphism (rh5-HTTLPR) genotype on peripheral serotonin transporter (5-HTT) regulation in response to a maternal/social separation and relocation stressor in infant rhesus macaques. We further tested the hypothesis that modulation of 5-HTT regulation by rearing and/or genotype is mediated by glucocorticoid (GC) availability. Fifty-three infant (3-4 months of age) rhesus macaques that were either nursery reared (NR) or mother reared (MR) were genotyped for rh5-HTTLPR. Infants were blood sampled within 2.5 h of maternal or social separation/relocation and again 5 h later. Infants were then administered dexamethasone, a synthetic GC and blood sampled 16.5 h later. 5-HTT RNA was quantified from peripheral blood mononuclear cells. Plasma cortisol was measured at all time points. The MR individuals upregulated 5-HTT significantly during maternal/social separation, while NR individuals did not. Concomitant increases in cortisol were not observed, but dexamethasone treatment stimulated 5-HTT expression regardless of genotype/rearing group, and 5-HTT expression in the post-stressor sample was correlated with plasma cortisol levels at all time points. Our data indicate that early experience exerted a strong influence on 5-HTT regulation during a stressor in infant rhesus macaques independent of rh5-HTTLPR genotype. We also showed that GCs may stimulate 5-HTT expression but that there likely exist faster-acting transcriptional regulators of 5-HTT that are in place as a function of experience.

Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys

“…In another study, Capitanio et al (38) demonstrated that 3-or 4-mo-old NR monkeys (similar to PR monkeys) showed significantly lower plasma cortisol levels 1 h following separation/relocation (stressor) than the age-matched MR controls. Similarly, Kinnally et al (39) demonstrated that 3-or 4-mo-old MR infants had significantly higher cortisol levels than the NR group 2.5 h following separation/relocation (stressor).…”

Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression

“…For instance, rhesus macaques that experienced high rates of rejection from their mothers soon after birth have lower levels of 5-HTT binding which is independent of 5-HTT genotype [55]. Another study compared SLC6A4 density in adulthood as a function of common natural variation in birth weight in rats [56].…”

Nonhuman Primate Research Contributions to Understanding Genetic and Environmental Influences on Phenotypic Outcomes across Development

“…The largest number of studies in this area have examined the effect of early infant rearing environment and genetic variation on subsequent behavioral, neurochemical, neuroendocrine phenotypes , Barr, Newman, Becker, Parker, et al, 2003Bennett et al, 2002;Champoux et al, 2002;Kinnally, Lyons, Abel, Mendoza, & Capitanio, 2008; for additional references and review, see below). Schneider and her colleagues have examined interplay between specific genetic variation and an early environmental manipulation with high clinical significance, prenatal alcohol exposure (Kraemer, Moore, Newman, Barr, & Schneider, 2008).…”