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The nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signal transduction pathway has been implicated in some forms of learning and memory. Recent findings suggest that inhibition of phosphodiesterase (PDE) enzymes that degrade cGMP may have memory-enhancing effects.

We examined whether treatment with sildenafil citrate, a PDE type 5 inhibitor, would attenuate a learning impairment induced by inhibition of NO synthase [60 mg/kg N ^ω-nitro-l-arginine methyl ester (l-NAME), i.p.].

Rats were pretrained in a one-way active avoidance of foot shock in a straight runway and, on the next day, received 15 training trials in a 14-unit T-maze, a task that has been shown to be sensitive to aging and impairment of central NO signaling systems. Combined treatments of …