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: Finally, we investigated the interaction between vortioxetine and the 5-HT3 receptor agonist m-CPBG (Figure 4). In 68% (11/16) of examined cells, local application of m-CPBG (20 µM) produced a transient increase in sIPCSs in a manner similar to that of 5-HT, suggesting that 5-HT3 receptors were involved in the 5-HT response (Figure 4(a1)). However, in most of the responding cells (9/11) the effect of m-CPBG was not repeatable after various (3–25 min) application intervals (Figure 4(a1), compare left and right panels). Even after a 25 min wash-out, there was a significant difference in response between the first and second applications of m-CPBG (Figures 4(a2) and 4(a3)). Due to this long-lasting desensitization of m-CPBG responses, the effect of vortioxetine was tested in a separate set of cells (Figures 4(b1)–4(b3), n=9). A 20–30 min pretreatment with vortioxetine (20 µM) blocked m-CPBG response in all recorded neurons. In the presence of vortioxetine, the effect of the first application of m-CPBG on both sIPSC frequency and amplitude was significantly attenuated (Figures 4(b2) and 4(b3), p<0.05 for both, unpaired Student’s t-test). Thus, vortioxetine blocked 5-HT and m-CPBG responses in a similar manner, suggesting that 5-HT3 receptor antagonism contributed to its inhibitory effect.
Affiliation: Lundbeck Research USA, Paramus, NJ, USA EDAL@lundbeck.com.