selection (marked with red line) evoked firing rate did not change over time Spontaneous Lopinavir firing activity was not changed due to Tianeptine application Next we investigated the effect of ip administered Tianeptine on AMPA evoked neuronal firing Intraperitoneal Tianeptine administration massively enhanced AMPA elicited firing activity within 10 min and this effect remained within the time frame of the recordings .
The average of the Tianeptine induced effect on AMPA-responses was calculated as the Agomelatine evoked responses of each recordings 30 min after ip administration (196 À 32%; n = 6 cells from 6 rats; P 005; Fig 2III) Intraperitoneal saline injection slightly increased evoked firing rate however following ip Tianeptine application evoked responses increased significantly (see Fig 2II for a representative recording) Besides enhancing evoked firing activity Tianeptine did not change the kinetics of the evoked spike trains as the evoked responses returned to the basal activity in about 10 s following AMPA ejection both before and after Tianeptine (Fig 2II Panel C)Modulating AMPA receptor function has been shown to be central in synaptic plasticity thus if Tianeptine positively modulate AMPA receptors then this may have an effect on long-term synaptic plasticity Therefore supplier Itraconazole we investigated the effects of Tianeptine on LTP and depotentiation of synaptic efficiency using murine hippocampal slices Following a 60 min.
Tianeptine administration period the stimulation intensity was reduced to evoke fEPSPs similar to the pre-administration level and LTP was evoked by theta-burst stimulation Tianeptine10 lM enhanced the initial phase of LTP (first 10 min; 213 À 21% n = 11 slices; P 005; Fig 3A) compared to control slices (181 À 16% n = 9 slices) Employing two-way price Fesoterodine ANOVA with post hoc Tukey¯s test showed that LTP after Tianeptine is significantly larger until 13 min after TBS (P 005) On the other hand 90 min after TBS the magnitude of potentiation was similar in Tianeptine treated (163 À 6%) and control slices (161 À 8%) In contrast treating the slices with 100 lMTianeptine did not alter the initial phase of LTP but it resulted in an impairment of the latter phase of potentiation (129 À 9% n = 6 slices vs 157 À 12% n = 4 slices; P 005; Fig 3B) Long-term depression (LTD) is another form of persistent synaptic plasticity where evoked fEPSPs remained depressed upon low frequency stimulation (LFS).
There was a trend that Tianeptine enhances LTD: the rate of LTD 30 min after LFS was 825 À 10% 25 min after LFS in the control slices (n = 4 slices) while in the 100 lM Tianeptine treated slices LTD was 73 À 11% (n = 6 slices; Fig 3C) This difference was not contusion significant although the first 6 min of LTD were significantly enhanced by Tianeptine (44 À 3% vs 63 À 6% for 6 min after LFS; two-way ANOVA with post hoc Tukey¯s test; P 005) If Tianeptine does not have any effect on NMDA receptors than it will not affect a form of plasticity that is dependent on NMDA receptors .