How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems

Dennis L. Murphy, Meredith A. Fox, Kiara R Timpano, Pablo R. Moya, Renee Ren-Patterson, Anne M. Andrews, Andrew Holmes, Klaus Peter Lesch, Jens R. Wendland

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species; an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene; and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species.

Original languageEnglish
Pages (from-to)932-960
Number of pages29
JournalNeuropharmacology
Volume55
Issue number6
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Genetic Association Studies
Serotonin
Genes
Serotonin Agents
Pharmacogenetics
Gene Deletion
Primates
Pharmacology
Phenotype
Brain

Keywords

  • Anxiety
  • Depression
  • Epistasis
  • Homeostasis
  • Obsessive-compulsive disorder
  • Serotonin transporter

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. / Murphy, Dennis L.; Fox, Meredith A.; Timpano, Kiara R; Moya, Pablo R.; Ren-Patterson, Renee; Andrews, Anne M.; Holmes, Andrew; Lesch, Klaus Peter; Wendland, Jens R.

In: Neuropharmacology, Vol. 55, No. 6, 01.11.2008, p. 932-960.

Research output: Contribution to journalArticle

Murphy, Dennis L. ; Fox, Meredith A. ; Timpano, Kiara R ; Moya, Pablo R. ; Ren-Patterson, Renee ; Andrews, Anne M. ; Holmes, Andrew ; Lesch, Klaus Peter ; Wendland, Jens R. / How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. In: Neuropharmacology. 2008 ; Vol. 55, No. 6. pp. 932-960.
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