Nitric oxide is involved in the memory facilitation induced by spermidine in rats

Rationale Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-d-aspartate receptor functions, which has been reported to facilitate memory formation.Objectives In the current study, we investigated the involvement of nitric oxide in the facilitatory effect of SPD on the memory of adult male Wistar rats in the inhibitory avoidance task.Results The coadministration of the nonspecific NOS inhibitor N ^G nitro-l-arginine methyl ester (l-NAME) (0.1 nmol, intrahippocampus) with spermidine (0.2 nmol), immediately after training, prevented the memory improvement caused by spermidine in the avoidance inhibitory task. Spermidine increased nitrite and nitrate levels (NO_X) in the hippocampus 30 min after its administration, and l-NAME coinjection prevented the stimulatory effect of spermidine on NO_X levels. The systemic injection of 7-nitroindazole (30 mg/kg, i.p.), 30 min before training, impaired memory and did not prevent spermidine-induced increase of NO_X levels in the hippocampus.Conclusions These results suggest that memory enhancement by spermidine is prevented by the nonspecific nitric oxide synthase inhibitor l-NAME.