(145 À 013) and after Tianeptine administration (143 À 004; n = 6 slices; Fig 1E) showing that Tianeptine likely has a postsynaptic site of action Similar results were reported in the CA3 by Kole et al (2002)Tianeptine enhances fEPSPs most probably via the modulation of postsynaptic excitatory ionotropic receptors thus next we asked which receptor is affected by Tianeptine We focused on NMDA and AMPA receptors by using specific antagonists Application of 50 lM of the AMPA receptor antagonist CNQX (6-cyano-7-nitroquixaline- 23-dione) caused a rapid and dramatic reduction in the amplitude of evoked fEPSPs Lacosamide (around 20%; n = 7 slices; Fig 1C) The remaining evoked responses were considered to be NMDA receptor-mediated because perfusion of an antagonist of the NMDA receptor completely blocked this fEPSP Applying 100 lM.
Tianeptine did not affect isolated NMDA receptor mediated fEPSPs indicating that Sorafenib Tianeptine does not modify NMDA receptor function in the CA1 (Fig 1C) Next we investigated the effects of Tianeptine on isolated AMPA responses We applied the non-competitive NMDA receptor antagonists MK-801 ((+)-5-methyl-1011-dihydro-5H-dibenzo[ad]cyclo hepten-510-imine maleate) in a concentration of 50 lM Perfusion of the drug onto slices had no significant effect on the amplitudes of evoked fEPSPs However applying CNQX completely diminished the evoked responses showing that upon MK-801 application the fEPSPs are AMPA receptor mediated (n = 4 slices)100 lM Tianeptine which significantly increased the amplitude of the isolated AMPA receptor mediated supplier Lopinavir fEPSPs (163 À 45% after 60 min administration n = 4 slices;
P 005; Fig 1D) indicating that Tianeptine enhances AMPA receptor mediated responses Moreover in order to test the effect of the NMDA receptor antagonist we applied theta-burst stimulation (TBS) for inducing LTP after the 60 min Tianeptine price glucitol administration period Long-term potentiation in the CA1 region of the hippocampus was shown to be NMDA receptor dependent thus we expected to detect impairment in LTPactivity from the dorsal CA1 Spike trains were evoked by applying either NMDA or AMPA by means of microiontophoresis in the very close vicinity of the recorded neuron First we focused on NMDA evoked neuronal firing .
Tianeptine was administered following at least five successive NMDA ejection epochs which triggered firing activity with no more than 15% difference in the spiking rate Evoked neuronal firing rate remained at the pre-Tianeptine level within the time frame of the recording (35¨C45 min) indicating that Tianeptine did not affect NMDA evoked neuronal responses (108 À 12%; n = 6 cells from five rats; Fig 2III) Panel A of Fig 2I shows a representative peristimulus histogram of the effect of ip applied Tianeptine on NMDA evoked neuronal activity The color coded peri-event time histogram with 100 ms bin trauma (Panel B) and the average of the firing rate of five successive trials before and 30 min after ip Tianeptine application shows that the 5-s NMDA.