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2 - Cellular and molecular alterations in animal models of serotonin transporter disruption: a comparison between developmental and adult stages

Published online by Cambridge University Press:  06 July 2010

By
Qian Li
Edited by
Allan V. Kalueff  and
Justin L. LaPorte
Allan V. Kalueff
Affiliation:
Georgetown University Medical Center
Justin L. LaPorte
Affiliation:
National Institute of Mental Health
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Summary

ABSTRACT

Serotonin transporter (SERT, 5-HTT) plays an important role in the regulation of emotional states. It is a target for the most widely used class of antidepressants, selective serotonin reuptake inhibitors (SSRIs), and is also related to a genetic factor underlying the pathogenesis of affective disorders. Humans with lower SERT expression genotypes show a higher neuroticism score and are more sensitive to stress, suggesting that low SERT expression during development may be a trigger for affective disorders. On the other hand, repeated administration of SSRIs reduces the stress response and treats affective disorders. These observations suggest that disruption of SERT function early in life and in adulthood produces different phenotypes. Thus, understanding the cellular and molecular mechanisms underlying these phenotypes will help us to understand the pathogenesis of affective disorders and develop better therapeutic approaches for their treatment. Animal models with altered SERT function provide useful tools for the studies concerning this purpose. This chapter is intended to overview current available data concerning the cellular and molecular alterations in the models in which SERT functions are disrupted during different developmental stages. We will focus on a comparison between constitutive SERT knock-out mice and repeated administration of SSRIs in adulthood. Furthermore, studies concerning the prenatal administration of SSRIs and genomic manipulation of SERT expression in adulthood are also discussed.

INTRODUCTION

The serotonin (5-HT) transporter (SERT, 5-HTT) functions as a 5-HT reuptake site to take extracellular 5-HT back into the nerve terminals and, therefore, terminates the action of 5-HT. Thus, the function of SERT is critical for controlling 5-HT activity, which plays an important role in emotional regulation.

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Experimental Models in Serotonin Transporter Research , pp. 43 - 77
Publisher: Cambridge University Press
Print publication year: 2010

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