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

26 Citations (Scopus)

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

Fingerprint

Excitatory Postsynaptic Potentials
Neurons
Pyramidal Cells
serotonin 6 receptor
Prefrontal Cortex
Inhibitory Concentration 50
Ligands
2-(5-chloro-2-methyl-1H-indol-3-yl)-N,N-dimethylethanamine

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission. / Tassone, Annalisa; Madeo, Graziella; Schirinzi, Tommaso; Vita, Daniela; Puglisi, Francesca; Ponterio, Giulia; Borsini, Franco; Pisani, Antonio; Bonsi, Paola.

In: Neuropharmacology, Vol. 61, No. 4, 09.2011, p. 632-637.

Research output: Contribution to journalArticle

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, vol. 61, no. 4, pp. 632-637. https://doi.org/10.1016/j.neuropharm.2011.05.004
Tassone A, Madeo G, Schirinzi T, Vita D, Puglisi F, Ponterio G et al. Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission. Neuropharmacology. 2011 Sep;61(4):632-637. https://doi.org/10.1016/j.neuropharm.2011.05.004
Tassone, Annalisa ; Madeo, Graziella ; Schirinzi, Tommaso ; Vita, Daniela ; Puglisi, Francesca ; Ponterio, Giulia ; Borsini, Franco ; Pisani, Antonio ; Bonsi, Paola. / Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission. In: Neuropharmacology. 2011 ; Vol. 61, No. 4. pp. 632-637.
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