Summary
Microiontophoresis of the 5-HT3 receptor agonists, 2-methyl-5-HT and phenylbiguanide (PBG), similar to the action of 5-HT, dose-dependently suppressed the firing of medial prefrontal cortical (mPFc) cells. There was little or no desensitization or tachyphylaxis to 5-HT or to the 5-HT3 receptor agonists. The continuous iontophoresis of 1 M magnesium chloride markedly attenuated or blocked the suppressant effect produced by electrical stimulation of the ascending 5-HT pathway but did not alter the action of 2-methyl-5-HT, suggesting that the action of 2-methyl-5-HT is direct. The suppressant action of 2-methyl-5-HT on mPFc cells was blocked by selective 5-HT3 receptor antagonists but not by other receptor antagonists. Furthermore, the S-enantiomer of zacopride was significantly more effective than the R-enantiomer in antagonising 2-methyl-5-HT indicating the steroselective antagonist action of zacopride.
In parallel to the electrophysiological studies, we have shown that both 2-methyl-5-HT and PBG mimicked the action of 5-HT in producing a significant increase in phosphoinositide (PI) turnover in fronto-cingulate and entorhinal cortical slices. The action of 2-methyl-5-HT and PBG on PI turnover was not altered by tetrodotoxin, suggesting that the action of these agonists is not dependent upon the impulse flow and that they do not alter PI turnover via interneurons. The stimulatory action of PBG and 2-methyl-5-HT was completely blocked by 5-HT3 receptor antagonists but not by other receptor antagonists. Moreover, S-zacopride was more potent than R-zacopride in blocking 2-methyl-5-HT.
These results suggest that 5-HT3 receptor agonists suppress the firing of mPFc neurons and stimulate PI turnover by a direct interaction with 5-HT3-like receptors. Furthermore, our data suggest that the biochemical and electrophysiological properties of 5-HT3-like receptors in the mPFc are different from those in the periphery.
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© 1991 Birkhäuser Verlag Basel/Switzerland
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Wang, R.Y., Ashby, C.R., Edwards, E. (1991). Characterization of 5-HT3-like Receptors in the Rat Cortex: Electrophysiological and Biochemical Studies. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_16
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DOI: https://doi.org/10.1007/978-3-0348-7259-1_16
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