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. 2014 Sep 30:3:199.
doi: 10.4103/2277-9175.142044. eCollection 2014.

Effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus of hippocampal formation in rats

Ghasem Zarei  1 , Parham Reisi  2 , Hojjatallah Alaei  1 , Shaghayegh Haghjooye Javanmard  3
Affiliations

Effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus of hippocampal formation in rats

Ghasem Zarei et al. Adv Biomed Res. .

Abstract

Background: Several studies have been shown that antidepressant drugs have contradictory effects on cognitive processes. Therefore, the aim of this study was to investigate the effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus (DG) of the hippocampal formation in rat.

Materials and methods: Experimental groups were the control, the fluoxetine, and amitriptyline. The rats were treated for 21 days and then, paired pulse facilitation/inhibition (PPF/I) and long-term potentiation (LTP) in perforant path-DG synapses were assessed (by 400 Hz tetanization). Field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured.

Results: The results of PPF/I showed that PS amplitude ratios were increased in 10-70 ms inter-stimulus intervals in the amitriptyline group compared to the control group. In the fluoxetine group, EPSP slope ratios were decreased in intervals 30, 40, and 50 ms inter-stimulus intervals compared to the control group. The PS-LTP was significantly lower in the fluoxetine and the amitriptyline groups with respect to the control group.

Conclusion: The results showed that fluoxetine and amitriptyline affect synaptic plasticity in the hippocampus and these effects is probably due to the impact on the number of active neurons.

Keywords: Amitriptyline; dentate gyrus; fluoxetine; hippocampus; synaptic plasticity.

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Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Schematic diagram of population spike (PS) and field excitatory post-synaptic potential (fEPSP) analysis. The PS parameters analyzed as: ([VB – VC] + [VD – VC])/2 and fEPSP slopeanalyzed as: AB slope
Figure 2
Figure 2
The effect of fluoxetine and amitriptyline on recurrent inhibition/facilitation in dentate gyrus of the hippocampus at (a) the population spike (PS) amplitude ratio, (percentage of mean PS2/PS1 ± SEM), and (b) excitatory post-synaptic potential slope ratio (percentage of mean EPSP2/EPSP1 ± SEM). (•P < 0.05, significant difference between the control and the amitriptyline groups; *P < 0.05, **P < 0.01 significant difference between the control and the fluoxetine groups (n = 6-7 in each group)
Figure 3
Figure 3
The effect of fluoxetine and amitriptyline on long-term potentiation (LTP) induction and maintenance in dentate gyrus of the hippocampus using 400 Hz tetanic stimulation at: (a) The magnitude of population spike-LTP and (b) excitatory post-synaptic potential slope-LTP. Data are plotted as the average percentage change from baseline responses. Values are % mean ± SEM. (•P < 0.05, ••P < 0.01, significant difference between the control and the amitriptyline groups; *P < 0.05, **P < 0.01 significant difference between the control and the fluoxetine groups (n = 6-7 in each group)
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