5HT3 receptors: Target for new antidepressant drugs

Deepali Gupta, Visakh Prabhakar, Mahesh Radhakrishnan

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic-pituitary-adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists.

Original languageEnglish (US)
Pages (from-to)311-325
Number of pages15
JournalNeuroscience and Biobehavioral Reviews
Volume64
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • 5HT receptors
  • CNS distribution
  • Depression
  • HPA-axis
  • Neurotransmitter
  • Oxidative stress

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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