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


1 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Physiology, School of Medicine; Applied Physiology Research Center; Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Physiology, School of Medicine; Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


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.


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