Zaprinast and Rolipram Enhances Spatial and Emotional Memory in the Elevated Plus Maze and Passive Avoidance Tests and Diminishes Exploratory Activity in Naive Mice

BACKGROUND Phosphodiesterase (PDE) inhibitors in the central nervous system have been shown to stimulate neuronal functions and increase neurogenesis in Alzheimer disease (AD) patients. MATERIAL/METHODS The aim of this study was to investigate the effects of zaprinast, a PDE5 inhibitor, and rolipram, a PDE4 inhibitor, on learning and memory in elevated plus maze (EPM) and passive avoidance (PA) tests in naive mice. Male Balb-c mice received short-term treatment with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) before the acquisition trial of the EPM and PA tests. The exploratory activity of the animals was also investigated in the Hughes box test. RESULTS Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased second-day latency compared to the control group in the EPM test, while only rolipram (0.1 mg/kg) significantly increased second-day latency in the PA test. Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased the number of entries to new areas and time spent in new areas in the Hughes box test. CONCLUSIONS Our study revealed that both zaprinast and rolipram enhanced spatial memory in EPM, while rolipram seemed to have more emotional memory-enhancing effects in the PA test compared to zaprinast. Both zaprinast and rolipram diminished exploratory activity in the Hughes box test, which can be attributed to the drugs' anxiogenic effects.