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
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Mentions: LTP was induced by stimulating the Schaeffer collateral fibers with a single train of theta-burst stimulation (TBS), as described in the Materials and Methods section. Following TBS, there was a long-lasting increase in the slope of the field excitatory post-synaptic potentials (fEPSPs) (Figure 5). The average LTP in vehicle-treated slices 60 min after TBS was 125±7% (n=17 slices from 12 animals). Perfusion of hippocampal slices with 20 µM vortioxetine for 30 min prior to TBS significantly increased the magnitude of LTP without affecting baseline transmission (Figure 5, p=0.0017, two-way ANOVA F(2,38)=7.548). The average LTP in vortioxetine-treated slices 60 min after TBS was 154±9% (n=14 slices from nine rats). In contrast, 10 µM escitalopram had no effect on LTP (Figure 5). The average LTP in escitalopram-treated slices 60 min after TBS was 127±5% (n=5 slices from four animals), which was very similar to the magnitude of LTP in vehicle-treated slices.
Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.