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 PDE(5) inhibitor, and rolipram, a PDE(4) 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.