Persistence is the most characteristic attribute of long-term memory (LTM). For memory persistence, a second late event of consolidation, that occurs around 12 h after the acquisition, is necessary. Although the N-methyl-d-aspartate (NMDA) receptor has been involved in the persistence of memory, whether endogenous modulators of the NMDA receptor actually modulate memory persistence is unknown. In the current study we investigated whether spermidine and arcaine, respectively agonist and antagonist of polyamine binding site at NMDA receptor, alter the persistence of the memory of contextual fear conditioning task in rats. While 12 h post-training administration of spermidine (10 and 30 mg/kg, i.p.) facilitated, arcaine (10 mg/kg, i.p.) impaired the memory of fear assessed 2 and 7 days after training. Arcaine (0.1 mg/kg) prevented the facilitatory effect of spermidine (10 mg/kg, i.p.), and spermidine (1 mg/kg), prevented the memory impairment induced by arcaine (10 mg/kg, i.p.) when tested 2 and 7 days after training. These results suggest that endogenous polyamines improve the persistence of fear memory.