Paracrine neurotransmission in the CNS: involvement of 5-HT

Trends Neurosci. 1999 Sep;22(9):377-82. doi: 10.1016/s0166-2236(99)01410-1.


While GABA and glutamate have an established synaptic function in the CNS, recent evidence suggests 5-HT neurotransmission is predominantly paracrine. As the amino-acid neurotransmitters interact with receptors that produce effects rapidly, electrophysiological approaches can be used to assess the time delay between transmitter release and the postsynaptic response directly. However, this approach cannot be used for studies of 5-HT-mediated neurotransmission, because the majority of its receptors react more slowly, so anatomical and voltammetrical approaches have been used to provide insight into 5-HT-mediated events. These studies have revealed that extrasynaptic receptors and transporters for 5-HT exist, and that 5-HT escapes readily from the synaptic cleft. Attenuation of 5-HT binding by 5-HT-receptor antagonists and 5-HT-uptake inhibitors does not affect the synaptic efflux elicited by transient stimuli, although the effects of such drugs are apparent at later time points. Once it is extrasynaptic, 5-HT has a concentration that is similar to those estimated to be optimal for receptor and transporter activation, and it can diffuse a few micrometers until removed by its transporter. These properties of 5-HT raise the possibility that it can act on receptors that are distant from its release site and function as a paracrine transmitter.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Central Nervous System / drug effects
  • Central Nervous System / physiology*
  • Humans
  • Neurotransmitter Agents / physiology
  • Paracrine Communication / drug effects
  • Paracrine Communication / physiology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Neurotransmitter Agents
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin