The effects of sildenafil on the hippocampal longterm potentiation in male rats

Introduction: 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. Methods: 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 μg/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. Results: The results showed that population spike amplitude and EPSP slope significantly increased after sildenafil administration (10μg/kg) following titanic stimulation compared with the saline group. However, the sildenafil (2μg/kg) and control groups showed no difference regarding population spike amplitude and EPSP slope. Sildenafil had no significant effects on recurrent inhibition. Conclusion: 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.