Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: Evidence from in vitro and animal-based studies

Stuart J. Warden, E. M. Haney

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations


The regulation of bone metabolism continues to be an area of intense investigation, with recent evidence indicating a potential contribution from the neural system. In particular, the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has been hypothesized to play a role in skeletal metabolism via its transporter (5-HTT). The 5-HTT is a plasma membrane transporter that is highly specific for the uptake of extracellular 5-HT, thereby facilitating the intracellular storage and/ or degradation of 5-HT. The 5-HTT is clinically important as it is the key target of pharmaceutical agents aimed at treating affective disorders, such as major depressive disorder. By antagonizing the 5-HTT, selective serotonin reuptake inhibitors (SSRIs) potentiate 5-HT activity and effectively relieve the symptoms of depression. However, questions have been raised regarding the potential skeletal effects of SSRIs given the recent identification of a functional 5-HTT and functional 5-HT receptors in bone cells. This paper discusses the preclinical evidence for the skeletal effects of 5-HT and the inhibition of the 5-HTT. In particular, it discusses the: (1) role of 5-HT and the function of the 5-HTT; (2) presence of functional 5-HTTs in bone; (3) potential sources and response mechanisms for 5-HT in bone, and; (4) in vitro and in vivo skeletal effects of 5-HT and 5-HTT inhibition.

Original languageEnglish (US)
Pages (from-to)121-132
Number of pages12
JournalJournal of Musculoskeletal Neuronal Interactions
Issue number2
StatePublished - Jun 2008


  • Antidepressants
  • Fluoxetine
  • Neurotransmitter
  • Osteoporosis
  • Prozac

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Orthopedics and Sports Medicine


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