Control of dorsal raphé 5-HT function by multiple 5-HT(1) autoreceptors: parallel purposes or pointless plurality?

Trends Neurosci. 2000 Oct;23(10):459-65. doi: 10.1016/s0166-2236(00)01631-3.

Abstract

The serotonergic cells of the dorsal raphé nucleus innervate much of the forebrain and are thought to be involved in the mechanism of action of antidepressants. Dysfunction of these cells might be involved in the neural mechanisms underlying depression and suicide. The traffic in pathways emanating from the dorsal raphé nucleus is controlled by 5-HT(1) autoreceptors. Until recently it was thought that the autoreceptors in the dorsal raphé nucleus were solely of the 5-HT(1A) subtype. In this article, we discuss evidence that the situation is more complex and that multiple 5-HT(1) subtypes govern different aspects of 5-HT function in the dorsal raphé nucleus presenting new therapeutic opportunities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology
  • Autoreceptors / classification
  • Autoreceptors / drug effects
  • Autoreceptors / physiology*
  • Dimerization
  • Guinea Pigs
  • Humans
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Ion Transport / drug effects
  • Ion Transport / physiology
  • Mice
  • Nerve Tissue Proteins / classification
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology*
  • Neurons / chemistry
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Protein Isoforms / drug effects
  • Protein Isoforms / physiology
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology*
  • Rats
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Second Messenger Systems / drug effects
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / pharmacology
  • Serotonin / physiology*
  • Serotonin Receptor Agonists / pharmacology
  • Spiperone / pharmacology
  • Sumatriptan / pharmacology

Substances

  • Antidepressive Agents, Second-Generation
  • Autoreceptors
  • CP 94253
  • HTR1B protein, human
  • Ion Channels
  • Nerve Tissue Proteins
  • Oxadiazoles
  • Piperazines
  • Protein Isoforms
  • Pyridines
  • Pyrimidines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • GR 127935
  • Serotonin
  • Spiperone
  • ipsapirone
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Sumatriptan