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.
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.
Liang
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State University of New York at Stony Brook, Department of Psychiatry and Behavioral Science, 11794-8790, USA.
Arvanov
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VL
Wang
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D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride