Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission

Annalisa Tassone, Graziella Madeo, Tommaso Schirinzi, Daniela Vita, Francesca Puglisi, Giulia Ponterio, Franco Borsini, Antonio Pisani, Paola Bonsi

Research output: Contribution to journalArticle

Abstract

We investigated the effect of 5-HT6 receptor subtype activation on glutamatergic transmission by means of whole-cell patch-clamp electrophysiological recordings from medium spiny neurons of the striatum and layer V pyramidal neurons of the prefrontal cortex. To this aim, we took advantage of a novel ligand, ST1936, showing nM affinity and agonist activity at the 5-HT6 receptor subtype. Our data show that 5-HT6 receptor activation by ST1936 reduces the frequency of spontaneous excitatory postsynaptic currents, with an IC50 of 1.3 μM. Moreover, 5-HT6 receptor activation also reduced the amplitude of spontaneous excitatory postsynaptic currents recorded from medium spiny neurons, suggesting a mechanism of action involving postsynaptic 5-HT6 receptors,as further confirmed by the paired-pulse analysis on evoked excitatory postsynaptic currents and by recordings of miniature glutamatergic events. The inhibitory effect of ST1936 on glutamatergic transmission was prevented by the selective 5-HT6 receptor antagonist SB258585 and mimicked by a different agonist, WAY-181187. Conversely, in the cortex ST1936 reduced the frequency, but not the amplitude, of spontaneous excitatory postsynaptic currents suggesting a presynaptic or indirect effect of the 5-HT6 receptor.

Original languageEnglish
Pages (from-to)632-637
Number of pages6
JournalNeuropharmacology
Volume61
Issue number4
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Cortex
  • Electrophysiology
  • EPSC
  • Medium spiny neuron
  • Serotonin
  • ST1936
  • Striatum

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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    Tassone, A., Madeo, G., Schirinzi, T., Vita, D., Puglisi, F., Ponterio, G., Borsini, F., Pisani, A., & Bonsi, P. (2011). Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission. Neuropharmacology, 61(4), 632-637. https://doi.org/10.1016/j.neuropharm.2011.05.004