Investigation of the Effect of Phosphodiesterase Type 9 Inhibitor PF-04447943 on Spatial Memory in Mice Using the Radial Arm Maze Test

Objective: Phosphodiesterase-9 (PDE9) inhibitors have attracted interest for improving cognitive function by increasing intracellular cGMP, an important mediator of learning and memory. The nitric oxide (NO)/cGMP pathway plays a key role in synaptic plasticity and hippocampal long-term potentiation (LTP), while inhibition of neuronal nitric oxide synthase (nNOS) impairs cognition. This study evaluated the effects of the PDE9 inhibitor PF-04447943 on spatial memory in mice and its interaction with nNOS inhibition induced by 7-nitroindazole (7-NI).Materials and Methods: Fifty male BALB/c mice (7–8 weeks old, 20–30 g) were randomly divided into five groups (n = 10 per group): control, PF-04447943 (1 and 3 mg/kg), 7-Nitroindazole (7-NI; 5 mg/kg), and a combination treatment group (5 mg/kg 7NI and 3 mg/kg PF-04447943). Drugs were administered intraperitoneally (i.p.). The radial arm maze test was used to measure spatial memory by recording arm reentries (errors) and task completion time (latency).Results: PF-04447943 (1 and 3 mg/kg, i.p.) significantly decreased the number of errors and latency at 3 mg/kg. The nNOS inhibitor 7-NI (5 mg/kg) significantly increased both values. The combined treatment group made notably fewer mistakes and had significantly reduced latency than the 7-NI group, yet their performance was not completely restored to control levels.Conclusions: Inhibiting PDE9 may enhance spatial memory and partially alleviate cognitive impairment associated with the NO pathway; however, intact NO signalling seems essential for complete cognitive recovery.