Abnormal Serotonin Levels During Perinatal Development Lead to Behavioral Deficits in Adulthood.

Relish Shah,Catia M. Teixeira,Emmanuelle Courtiol,Francisco X. Castellanos

doi:10.3389/fnbeh.2018.00114

Abstract

Serotonin (5-HT) is one of the best-studied modulatory neurotransmitters with ubiquitous presynaptic release and postsynaptic reception. 5-HT has been implicated in a wide variety of brain functions, ranging from autonomic regulation, sensory perception, feeding and motor function to emotional regulation and cognition. The role of this neuromodulator in neuropsychiatric diseases is unquestionable with important neuropsychiatric medications, e.g., most antidepressants, targeting this system. Importantly, 5-HT modulates neurodevelopment and changes in its levels during development can have life-long consequences. In this mini-review, we highlight that exposure to both low and high serotonin levels during the perinatal period can lead to behavioral deficits in adulthood. We focus on three exogenous factors that can change 5-HT levels during the critical perinatal period: dietary tryptophan depletion, exposure to serotonin-selective-reuptake-inhibitors (SSRIs) and poor early life care. We discuss the effects of each of these on behavioral deficits in adulthood.

Highlights

Serotonin (5-hydroxytryptamine, 5-HT) is a classic and well-studied neuromodulator
In addition to being implicated in various functions ranging from autonomic regulation to emotions in the adult, 5-HT has a key role in neurodevelopment
Manipulations that either increase or decrease 5-HT levels during development have been shown to lead to behavioral deficits in the adult (Table 1). These studies suggest that optimal levels of 5-HT must be maintained during development and that any deviations from these optimal levels, in either direction, can lead to longlasting behavioral deficits (Figure 1). In this mini-review, we focus on three distinct exogenous factors, diet, pharmacological exposure and early-life care, which affect serotonin levels during the perinatal period and have behavioral consequences in adulthood

Summary

INTRODUCTION

Serotonin (5-hydroxytryptamine, 5-HT) is a classic and well-studied neuromodulator. In addition to being implicated in various functions ranging from autonomic regulation to emotions in the adult, 5-HT has a key role in neurodevelopment. These mice showed depression-like behaviors with decreased sucrose consumption and increased immobility time in the forced-swim-test (Rebello et al, 2014) These deleterious effects were specific to SSRIs. Postnatal treatment with fluoxetine, clomipramine and citalopram all produced emotional behavioral deficits in mice while administration of the norepinephrine transporter inhibitor, desipramine, did not (Ansorge et al, 2008). Early life maternal separation or abuse induce modifications of serotonergic signaling (for example increased 5-HT level or increased 5-HT2 receptor expression) that are correlated with later-on maladaptive behaviors such as deficits in social interactions and anxiety-like and depressive-like behaviors in adulthood

Findings

DISCUSSION

CONCLUSION