Intrahippocampal spermidine administration improves inhibitory avoidance performance in rats

Polyamines are polycations present at high concentrations in the mammalian brain. We investigated the effect of an intrahippocampal infusion of spermidine, a polyamine agonist, immediately post-training on the inhibitory avoidance learning paradigm in rats. Bilateral intrahippocampal microinjection of spermidine (0.02-20 nmol) caused an increase in test step-down latencies at low concentrations. Administration of arcaine (0.002-0.2 nmol), an antagonist of the N-methyl-D-aspartate (NMDA) receptor polyamine binding site, did not modify the test step-down latencies. In contrast, co-administration of arcaine and spermidine completely reversed the facilitatory effect of spermidine on the test step-down latencies. These results provide evidence that polyamines may be involved in learning and memory modulation.