Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat

Synapse. 2000 Jun 1;36(3):205-21. doi: 10.1002/(SICI)1098-2396(20000601)36:3<205::AID-SYN5>3.0.CO;2-D.


The present study evaluated, via a combined electrophysiological and dialysis approach, the potential influence of serotonin (5-HT)(2C) as compared to 5-HT(2A) and 5-HT(2B) receptors on dopaminergic, adrenergic, and serotonergic transmission in frontal cortex (FCX). Whereas the selective 5-HT(2A) antagonist MDL100,907 failed to modify extracellular levels of dopamine (DA), noradrenaline (NA) or 5-HT simultaneously quantified in single dialysate samples of freely-moving rats, the 5-HT(2B)/5-HT(2C) antagonist SB206,553 dose-dependently increased levels of DA and NA without affecting those of 5-HT. This action was attributable to 5-HT(2C) receptor blockade inasmuch as the selective 5-HT(2C) antagonist SB242,084 likewise increased FCX levels of DA and NA, whereas the selective 5-HT(2B) antagonist SB204,741 was ineffective. Further, the preferential 5-HT(2C) receptor agonist Ro60-0175 dose-dependently depressed FCX levels of DA. The suppressive influence of 5-HT(2C) receptors on DA release was also expressed on mesolimbic and nigrostriatal dopaminergic pathways, in that levels of DA in nucleus accumbens and striatum were likewise reduced by Ro60-0175 and elevated, though less markedly, by SB206,553. In line with the above findings, Ro60-0175 dose-dependently decreased the firing rate of ventrotegmental dopaminergic and locus coeruleus (LC) adrenergic perikarya, whereas their activity was dose-dependently enhanced by SB206,553. Furthermore, SB206,553 transformed the firing pattern of ventrotegmental dopaminergic neurons into a burst mode. In contrast to SB206,553, MDL100,907 had little affect on the firing rate of dopaminergic or adrenergic neurons. In conclusion, as compared to 5-HT(2A) and 5-HT(2B) receptors, 5-HT(2C) receptors exert a tonic, suppressive influence on the activity of mesocortical - as well as mesolimbic and nigrostriatal - dopaminergic pathways, likely via indirect actions expressed at the level of their cell bodies. Frontocortical adrenergic, but not serotonergic, transmission is also tonically suppressed by 5-HT(2C) receptors.

MeSH terms

  • Animals
  • Cerebral Cortex / physiology*
  • Corpus Striatum / metabolism
  • Dialysis
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Electrophysiology
  • Epinephrine / metabolism
  • Epinephrine / physiology*
  • Extracellular Space / metabolism
  • Frontal Lobe / metabolism
  • Locus Coeruleus / cytology
  • Locus Coeruleus / physiology
  • Male
  • Neurons / physiology
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / physiology*
  • Serotonin / metabolism
  • Serotonin / physiology
  • Tegmentum Mesencephali / cytology
  • Tegmentum Mesencephali / metabolism


  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin
  • Dopamine
  • Epinephrine