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: Consistent with published results, local application of 5-HT significantly increased sIPSCs recorded from CA1 pyramidal cells (Figure 1(a1)). Approximately 85% of cells responded to 5-HT with a burst-like enhancement in sIPSC frequency and amplitude. Only those cells were included in the analysis of this study (n=24 cells). The effect of 5-HT was always transient and lasted for ~60 s (Figures 1(a1)–(a3)). Because of rapid desensitization, 5-HT was applied focally onto the surface of the slice via a fast speed perfusion system. Although fast desensitizing, 5-HT responses were repeatable after a 3–5 min washout (data not shown). Frequency and amplitude analyses for 60 s of recordings for 10 representative cells following 5-HT application are shown in Figures 1(a2) and 1(a3). Peak 5-HT response was observed within the first 15 s, during which sIPSC frequency and amplitude were increased by 301±34% and 261±26%, respectively (n=24 cells).
Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.