Differential Effects of Sildenafil (Viagra) on Processing Steps of Spatial Learning and Memory in Rat

Background: Sildenafil (Viagra) has been introduced to treat erectile dysfunction by acting as phosphodiesterase 5 inhibitor and hence accumulation of guanosine cyclic monophosphate (cGMP). On the other hands, the nitric oxide/cGMP signaling pathway has crucial role in synaptic plasticity processes like long-term potentiation (LTP) in the central nervous system considered as a model of learning and memory. Objectives: The aim of the present study was to determine the effects of sildenafil on different stages of spatial learning and memory of rat using radial maze. Materials and Methods: The effects of pre-training, pre-retrieval oral administration or post-training i.p. injection of sildenafil (10 mg/kg) in radial maze task were investigated. Results: Pre-training and post-training administration of sildenafil impaired radial maze task. Pre-retrieval injection of sildenafil decreased reference memory and working memory errors. Therefore, sildenafil impaired acquisition and consolidation of spatial learning and memory but improved retrieval of spatial memory in radial maze. Conclusions: Sildenafil has differential effects on the spatial learning and memory processing. It seems this result is due to accumulation of cGMP in the neural structures related to learning and memory processing. As different neural structures are involved in different learning and memory tasks, these results might be due to the different actions of cGMP in different structures of brain.