Send to

Choose Destination
Psychopharmacology (Berl). 2006 Jan;183(4):439-45. Epub 2005 Nov 18.

Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition.

Author information

Behavioral Neuroscience Section, Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.



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(omega)-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 L-NAME or saline and sildenafil (1.0, 1.5, 3.0, or 4.5 mg/kg, i.p.) or vehicle were given 30 and 15 min before training, respectively. Behavioral measures of performance included entries into incorrect maze sections (errors), run time from start to goal (latency), shock frequency, and shock duration.


Statistical analysis revealed that L-NAME impaired maze performance and that sildenafil (1.5 mg/kg) significantly attenuated this impairment. Control experiments revealed that administration of L-NAME alone did not significantly increase latencies in a one-way active avoidance test and that different doses of sildenafil alone did not significantly alter complex maze performance.


The results indicate that sildenafil may improve learning by modulating NO-cGMP signal transduction, a pathway implicated in age-related cognitive decline and neurodegenerative disease.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center