en Blood and Immune System Blood and Immune System Experimental research article Experimental research article <div style="text-align: justify;"><span class="fontstyle0"><strong>Introduction:</strong> </span><span class="fontstyle2">The hippocampal nitric oxide/cGMP signaling pathway plays a crucial role in memory processing. Phosphodiesterase interacts with this signaling pathway. There are controversial reports regarding the effect of sildenafil, a phosphodiesterase inhibitor, on learning and memory. Therefore, the effects of acute administration (intrahippocampal/ intra-dentate gyrus injection) of sildenafil on long-term potentiation (LTP) of rats were investigated. </span><span class="fontstyle0"><strong>Methods:</strong> </span><span class="fontstyle2">The rats were anesthetized with urethane and placed in a stereotaxic device for field potential recording. After ensuring a steady-state baseline response, a single intraperitoneal injection of saline or sildenafil (2 and10 &micro;g/kg) was done. The population spike amplitude, the excitatory postsynaptic potentials (EPSPs) slope and paired-pulse stimuli (as an inhibitory interneuron) were compared between groups. </span><span class="fontstyle0"><strong>Results:</strong> </span><span class="fontstyle2">The results showed that population spike amplitude and EPSP slope significantly increased after sildenafil administration (10&micro;g/kg) following titanic stimulation compared with the saline group. However, the sildenafil (2&micro;g/kg) and control groups showed no difference regarding population spike amplitude and EPSP slope. Sildenafil had no significant effects on recurrent inhibition. </span><span class="fontstyle0"><strong>Conclusion:</strong> </span><span class="fontstyle2">The obtained results indicated that acute administration of sildenafil improved LTP via direct effects on the hippocampus of intact rats. Thus, sildenafil may enhance learning and memory processing by modulating the hippocampal synapse.</span></div> Sildenafil, Phosphodiesterase inhibitor, Long term potentiation, Hippocampus 138 144 http://ppj.phypha.ir/browse.php?a_code=A-10-1336-3&slc_lang=en&sid=1 Siamak Shahidi 3200319475328460030910 3200319475328460030910 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Mina Vishteh 3200319475328460030911 3200319475328460030911 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Alireza komaki 3200319475328460030912 3200319475328460030912 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Reihaneh Sadeghian sadeghian.r@skums.ac.ir 3200319475328460030913 3200319475328460030913 Yes Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran