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