Differential effect of the PDE5 inhibitors, sildenafil and zaprinast, in aging- and lipopolysaccharide-induced cognitive dysfunction in mice

Abstract

In the present study, we have investigated the effects of exogenously administered cyclic GMP-specific PDE5 inhibitors, sildenafil and zaprinast, on cognitive performance in aged- and lipopolysaccharide (LPS)-treated mice using passive avoidance and plus-maze tasks. Aged and LPS-treated mice showed poor retention of memory in step-through passive avoidance and plus-maze task. Administration of PDE5 inhibitors reversed the age-induced retention deficits in both of the test paradigms. Also, PDE5 inhibitors on acute administration in young mice showed improvement in memory retention when tested in both of the paradigms. However, the effect of two PDE5 inhibitors was more pronounced in aged animals than that in young mice. PDE5 inhibitors enhanced the retention deficits in LPS-treated animals, which might be due to elevation of cGMP levels caused by sildenafil and zaprinast. In conclusion, these results indicated that differential effects of PDE5 inhibitors in aging and LPS-treated mice, but its prudential effect in aged mice may suggest new therapeutic use of these compounds. © 2004 Wiley-Liss, Inc.