5-HT3-like receptors in the rat medial prefrontal cortex: an electrophysiological study

Brain Res. 1991 Jun 7;550(2):181-91. doi: 10.1016/0006-8993(91)91316-s.


In this study, we have identified and characterized 5-HT3-like receptors in the rat medial prefrontal cortex (mPFc), an area with a moderate density of 5-HT3 binding sites, using the techniques of single unit recording and microiontophoresis. The microiontophoresis of the 5-HT3 receptor agonist 2-methylserotonin (2-Me-5HT), similar to the action of 5-HT, produced a current-dependent (10-80 nA) suppression of the firing rate of both spontaneously active and glutamate (GLU)-activated (quiescent) mPFc cells. Phenylbiguanide (PBG), another 5-HT3 receptor agonist, suppressed the firing rate of mPFc cells but was less effective compared to 2-Me-5HT. The continuous iontophoresis (10-20 min) of 1 M magnesium chloride markedly attenuated the suppressant effect produced by electrical stimulation of the ascending 5-HT pathway, but did not alter 2-Me-5HT's action, suggesting that the action of 2-Me-5HT is a direct one. The suppressant action of 2-Me-5HT on mPFc cells was blocked by a number of structurally diverse and selective 5-HT3 antagonists, with a rank order of effectiveness as follows: ICS 205930 = (+/-)-zacopride greater than granisetron = ondansetron = LY 278584 greater than MDL 72222. Furthermore, the intravenous administration of (+/-)-zacopride antagonized the action of 2-Me-5HT and PBG on mPFc cells. In contrast to the effects of the 5-HT3 receptors antagonists, other receptor antagonists such as metergoline (5-HT1A,1B,1C.2), (+/-)-pindolol (5-HT1A,1B, beta), SCH 23390 (5-HT1C.2, D1), l-sulpiride (D2) or SR 95103 (GABAA) failed to block 2-Me-5HT's action. These results combined suggest that 2-Me-5HT's suppressive action on mPFc cells is mediated directly by 5-HT3-like receptors.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Benzamides / pharmacology
  • Biguanides / pharmacology
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Cerebral Cortex / anatomy & histology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Evoked Potentials / drug effects
  • Glutamates / pharmacology
  • Glutamic Acid
  • Hypoglycemic Agents / pharmacology
  • Magnesium Chloride / pharmacology
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology*


  • Benzamides
  • Biguanides
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Glutamates
  • Hypoglycemic Agents
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Magnesium Chloride
  • Serotonin
  • Glutamic Acid
  • 2-methyl-5-HT
  • zacopride
  • phenyl biguanide