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Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

Dale E, Zhang H, Leiser SC, Xiao Y, Lu D, Yang CR, Plath N, Sanchez C - J. Psychopharmacol. (Oxford) (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.

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Related in: MedlinePlus

Vortioxetine enhanced theta burst long-term potentiation (LTP) in hippocampal slices.Representative traces of field excitatory post-synaptic potential (fEPSP) recordings from vehicle-treated, vortioxetine-treated and escitalopram-treated slices are shown on top of the graph. Each trace is the mean of five sweeps taken either immediately before (dashed line marked with (1) or 50 min after (solid line marked with (2)) theta-burst stimulation (TBS). TBS, marked with an arrow in the time course graph, induced a long-lasting increase in the slopes of fEPSPs. For each time point, fEPSP slopes were calculated from either vehicle-treated (n=17 slices from 12 animals), vortioxetine-treated (n=14 from nine animals) or escitalopram-treated slices (n=5 slices from four animals) and expressed as % of baseline. Data are shown as the mean±standard error of the mean (SEM). Perfusion of hippocampal slices with vortioxetine for 30 min prior to TBS increased LTP without affecting baseline transmission (p=0.0017 vortioxetine vs vehicle, two-way analysis of variance (ANOVA) F(2,38)=7.548)). Escitalopram had no effect on LTP (p>0.05).
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fig5-0269881114543719: Vortioxetine enhanced theta burst long-term potentiation (LTP) in hippocampal slices.Representative traces of field excitatory post-synaptic potential (fEPSP) recordings from vehicle-treated, vortioxetine-treated and escitalopram-treated slices are shown on top of the graph. Each trace is the mean of five sweeps taken either immediately before (dashed line marked with (1) or 50 min after (solid line marked with (2)) theta-burst stimulation (TBS). TBS, marked with an arrow in the time course graph, induced a long-lasting increase in the slopes of fEPSPs. For each time point, fEPSP slopes were calculated from either vehicle-treated (n=17 slices from 12 animals), vortioxetine-treated (n=14 from nine animals) or escitalopram-treated slices (n=5 slices from four animals) and expressed as % of baseline. Data are shown as the mean±standard error of the mean (SEM). Perfusion of hippocampal slices with vortioxetine for 30 min prior to TBS increased LTP without affecting baseline transmission (p=0.0017 vortioxetine vs vehicle, two-way analysis of variance (ANOVA) F(2,38)=7.548)). Escitalopram had no effect on LTP (p>0.05).

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.


Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

Dale E, Zhang H, Leiser SC, Xiao Y, Lu D, Yang CR, Plath N, Sanchez C - J. Psychopharmacol. (Oxford) (2014)

Vortioxetine enhanced theta burst long-term potentiation (LTP) in hippocampal slices.Representative traces of field excitatory post-synaptic potential (fEPSP) recordings from vehicle-treated, vortioxetine-treated and escitalopram-treated slices are shown on top of the graph. Each trace is the mean of five sweeps taken either immediately before (dashed line marked with (1) or 50 min after (solid line marked with (2)) theta-burst stimulation (TBS). TBS, marked with an arrow in the time course graph, induced a long-lasting increase in the slopes of fEPSPs. For each time point, fEPSP slopes were calculated from either vehicle-treated (n=17 slices from 12 animals), vortioxetine-treated (n=14 from nine animals) or escitalopram-treated slices (n=5 slices from four animals) and expressed as % of baseline. Data are shown as the mean±standard error of the mean (SEM). Perfusion of hippocampal slices with vortioxetine for 30 min prior to TBS increased LTP without affecting baseline transmission (p=0.0017 vortioxetine vs vehicle, two-way analysis of variance (ANOVA) F(2,38)=7.548)). Escitalopram had no effect on LTP (p>0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4230848&req=5

fig5-0269881114543719: Vortioxetine enhanced theta burst long-term potentiation (LTP) in hippocampal slices.Representative traces of field excitatory post-synaptic potential (fEPSP) recordings from vehicle-treated, vortioxetine-treated and escitalopram-treated slices are shown on top of the graph. Each trace is the mean of five sweeps taken either immediately before (dashed line marked with (1) or 50 min after (solid line marked with (2)) theta-burst stimulation (TBS). TBS, marked with an arrow in the time course graph, induced a long-lasting increase in the slopes of fEPSPs. For each time point, fEPSP slopes were calculated from either vehicle-treated (n=17 slices from 12 animals), vortioxetine-treated (n=14 from nine animals) or escitalopram-treated slices (n=5 slices from four animals) and expressed as % of baseline. Data are shown as the mean±standard error of the mean (SEM). Perfusion of hippocampal slices with vortioxetine for 30 min prior to TBS increased LTP without affecting baseline transmission (p=0.0017 vortioxetine vs vehicle, two-way analysis of variance (ANOVA) F(2,38)=7.548)). Escitalopram had no effect on LTP (p>0.05).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.

Show MeSH
Related in: MedlinePlus