Inhibition of NMDA-receptor mediated response in the rat medial prefrontal cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT: intracellular studies

Synapse. 1998 Jul;29(3):257-68. doi: 10.1002/(SICI)1098-2396(199807)29:3<257::AID-SYN8>3.0.CO;2-5.


The techniques of intracellular recording and single-electrode voltage-clamp were used to study the effect of serotonin (5-HT) and the selective 5-HT3 receptor agonist SR 57227A on N-methyl-D-aspartic acid (NMDA)-evoked responses in pyramidal cells of the rat medial prefrontal cortex (mPFC) in in vitro brain slice preparations. Bath application of 5-HT or SR 57227A produced a concentration-dependent inhibition of NMDA-induced membrane depolarization, action potentials, and inward current. The depressant action of 5-HT and SR 57227A had a slow onset and showed no signs of receptor desensitization. This action was markedly attenuated or completely blocked by the selective 5-HT3 receptor antagonists granisetron and BRL 46470A, but not other receptor antagonists. In addition to inhibiting NMDA-evoked responses, SR 57227A also depressed significantly pharmacologically isolated, NMDA receptor-mediated, monosynaptic excitatory postsynaptic currents (EPSCs) elicited by electrical stimulation of the forceps minor; this inhibitory action was blocked by BRL 46470A but not other 5-HT receptor antagonists. Perfusion of Ca2+-free or low Ca2+ plus Cd2+ artificial cerebrospinal fluid prevented electrical stimulation-induced EPSCs, but did not affect the inhibitory action of 5-HT and SR 57227A. In conclusion, we demonstrate for the first time that 5-HT and SR 57227A interact with 5-HT3-like receptors to produce a direct inhibitory action on NMDA receptor-mediated response in pyramidal cells of the mPFC.

Publication types

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

MeSH terms

  • Animals
  • Electric Stimulation
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Intracellular Membranes / physiology
  • Male
  • Piperidines / pharmacology*
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects*
  • Pyramidal Cells / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Synaptic Transmission / drug effects


  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin
  • 4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride