Activation of 5-HT6 receptors inhibits corticostriatal glutamatergic transmission

作者：Tassone Annalisa; Madeo Graziella; Schirinzi Tommaso; Vita Daniela; Puglisi Francesca; Ponterio Giulia; Borsini Franco; Pisani Antonio^*; Bonsi Paola

来源：Neuropharmacology, 2011, 61(4): 632-637.

DOI：10.1016/j.neuropharm.2011.05.004

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

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 mu M. 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.

• 出版日期2011-9