Limits...
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.

Show MeSH

Related in: MedlinePlus

Vortioxetine increased frontal cortical theta power in in vivo electroencephalography (EEG) recordings. (a1) Total relative theta power are shown for each treatment for every 15 min from 0–180 min postdose. A treatment effect was observed for vortioxetine (VOR), but not escitalopram (p=0.0226, one-way analysis of variance (ANOVA) F(65,497)=1.4180). (a2) Pharmacologically-induced changes in EEG recordings were quantified by averaging the 10 s bins constituting 15–75 min before (baseline) and 45–90 min post-drug treatment. Theta power was expressed as the percentage change from baseline. Bar graphs represent the mean±standard error of the mean (SEM) (n=9 rats per condition). A negative value indicates a decrease in EEG power from baseline. Vortioxetine at 5.0 and 10 mg/kg significantly increased theta power (*p<0.05, post-dose versus vehicle, one-way analysis of variance (ANOVA) with least significant difference (LSD) post-hoc comparison). Escitalopram at 2.0 mg/kg had no effect on theta power.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6-0269881114543719: Vortioxetine increased frontal cortical theta power in in vivo electroencephalography (EEG) recordings. (a1) Total relative theta power are shown for each treatment for every 15 min from 0–180 min postdose. A treatment effect was observed for vortioxetine (VOR), but not escitalopram (p=0.0226, one-way analysis of variance (ANOVA) F(65,497)=1.4180). (a2) Pharmacologically-induced changes in EEG recordings were quantified by averaging the 10 s bins constituting 15–75 min before (baseline) and 45–90 min post-drug treatment. Theta power was expressed as the percentage change from baseline. Bar graphs represent the mean±standard error of the mean (SEM) (n=9 rats per condition). A negative value indicates a decrease in EEG power from baseline. Vortioxetine at 5.0 and 10 mg/kg significantly increased theta power (*p<0.05, post-dose versus vehicle, one-way analysis of variance (ANOVA) with least significant difference (LSD) post-hoc comparison). Escitalopram at 2.0 mg/kg had no effect on theta power.

Mentions: Vortioxetine (tested at 0.1, 1.0, 3.0, 5.0 and 10 mg/kg, s.c.) produced a significant dose-response effect on frontal cortical theta power during the active wake state in EEG recordings (Figure 6; Leiser et al., 2014). The effect was observed in the relative theta power following treatment (Figure 6(a1)). To quantify this effect, theta power was compared pre- (15–75 min before) and post- (45–90 min after) dose using each rat as its own control and plotted as a percent change. The 45–90 min time bin was chosen to ensure that sample EEG data were taken when the drug was onboard and the data were not confound by behavioral change due to dosing. There was a significant treatment effect in theta power during this time (Figure 6(a2), p=0.00062, one-way ANOVA F(14,113)=2.9964). At 5.0 and 10 mg/kg, vortioxetine significantly increased theta (p<0.05, post-dose vs vehicle, LSD post-hoc comparison). In contrast, escitalopram (2.0 mg/kg, s.c.) had no effect on theta power (Figure 6(a2)).


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 increased frontal cortical theta power in in vivo electroencephalography (EEG) recordings. (a1) Total relative theta power are shown for each treatment for every 15 min from 0–180 min postdose. A treatment effect was observed for vortioxetine (VOR), but not escitalopram (p=0.0226, one-way analysis of variance (ANOVA) F(65,497)=1.4180). (a2) Pharmacologically-induced changes in EEG recordings were quantified by averaging the 10 s bins constituting 15–75 min before (baseline) and 45–90 min post-drug treatment. Theta power was expressed as the percentage change from baseline. Bar graphs represent the mean±standard error of the mean (SEM) (n=9 rats per condition). A negative value indicates a decrease in EEG power from baseline. Vortioxetine at 5.0 and 10 mg/kg significantly increased theta power (*p<0.05, post-dose versus vehicle, one-way analysis of variance (ANOVA) with least significant difference (LSD) post-hoc comparison). Escitalopram at 2.0 mg/kg had no effect on theta power.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6-0269881114543719: Vortioxetine increased frontal cortical theta power in in vivo electroencephalography (EEG) recordings. (a1) Total relative theta power are shown for each treatment for every 15 min from 0–180 min postdose. A treatment effect was observed for vortioxetine (VOR), but not escitalopram (p=0.0226, one-way analysis of variance (ANOVA) F(65,497)=1.4180). (a2) Pharmacologically-induced changes in EEG recordings were quantified by averaging the 10 s bins constituting 15–75 min before (baseline) and 45–90 min post-drug treatment. Theta power was expressed as the percentage change from baseline. Bar graphs represent the mean±standard error of the mean (SEM) (n=9 rats per condition). A negative value indicates a decrease in EEG power from baseline. Vortioxetine at 5.0 and 10 mg/kg significantly increased theta power (*p<0.05, post-dose versus vehicle, one-way analysis of variance (ANOVA) with least significant difference (LSD) post-hoc comparison). Escitalopram at 2.0 mg/kg had no effect on theta power.
Mentions: Vortioxetine (tested at 0.1, 1.0, 3.0, 5.0 and 10 mg/kg, s.c.) produced a significant dose-response effect on frontal cortical theta power during the active wake state in EEG recordings (Figure 6; Leiser et al., 2014). The effect was observed in the relative theta power following treatment (Figure 6(a1)). To quantify this effect, theta power was compared pre- (15–75 min before) and post- (45–90 min after) dose using each rat as its own control and plotted as a percent change. The 45–90 min time bin was chosen to ensure that sample EEG data were taken when the drug was onboard and the data were not confound by behavioral change due to dosing. There was a significant treatment effect in theta power during this time (Figure 6(a2), p=0.00062, one-way ANOVA F(14,113)=2.9964). At 5.0 and 10 mg/kg, vortioxetine significantly increased theta (p<0.05, post-dose vs vehicle, LSD post-hoc comparison). In contrast, escitalopram (2.0 mg/kg, s.c.) had no effect on theta power (Figure 6(a2)).

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