Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.
Bottom Line: Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism.In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures.Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus.
Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.Show MeSH
Related in: MedlinePlus
License 1 - License 2 - License 3
Mentions: The effect of vortioxetine was only studied in cells that responded to 5-HT. In these cells, bath application of 20 µM vortioxetine did not affect baseline sIPSCs (n=15, data not shown), but largely suppressed the 5-HT-mediated increase in sIPSC frequency and amplitude (Figure 2, p<0.05 for both, paired Student’s t-test). Vortioxetine required at least 15 min of application to achieve its maximal effect, which lasted for >30 min. We never observed a complete wash-out of the vortioxetine response, most likely due to the fact that vortioxetine is >99% protein bound in rat brain tissue (Sanchez et al., 2014) and thus is probably difficult to wash-out. The inhibitory effect of vortioxetine on sIPSCs was observed in 14 of the 15 cells tested (Figures 2(b1) and 2(c1)). To control for a possible desensitization of 5-HT response, vortioxetine was applied after the third application of 5-HT to a subset of cells. Under these conditions, vortioxetine still fully inhibited 5-HT responses, indicating that desensitization could not explain the inhibitory effect seen with vortioxetine (n=3, data not shown).
Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.