Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI

Eur J Pharmacol. 1991 Jul 9;199(3):349-55. doi: 10.1016/0014-2999(91)90499-g.


Systemic, intra-raphe and microiontophoretic administration of the 5-hydroxytryptamine (5-HT)1C/5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) inhibited the firing of 5-HT neurones in the dorsal raphe. DOI administered systemically and directly into the raphe also decreased the extracellular concentration of 5-hydroxytryptamine (5-HT) in the frontal cortex. In contrast, the administration of DOI directly into the frontal cortex did not significantly alter the concentration of frontal cortical extracellular 5-HT. The reduction of the firing rate of 5-HT neurons in the dorsal raphe and extracellular 5-HT concentration in the frontal cortex induced by systemic administration of DOI could not be blocked by the 5-HT2 antagonist ketanserin, ritanserin (5-HT2/5-HT1C antagonist) or the putative 5-HT1A antagonist, pindolol. These results suggest that the inhibition of 5-HT neuronal firing seen with administration of DOI is mediated via an action within the dorsal raphe and at least in close proximity to the 5-HT neurone cell bodies. The decrease in frontal cortical extracellular concentration of 5-HT release was not due to a direct action in the frontal cortex itself and may possibly be as a result of the decrease in the firing rate of the 5-HT neurones in the dorsal raphe. The mechanism of action of DOI to produce these effects is, however, unclear and warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology*
  • Animals
  • Cerebral Cortex / physiology
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Serotonin / physiology*


  • Amphetamines
  • Serotonin
  • 4-iodo-2,5-dimethoxyphenylisopropylamine