Systemic administration of polyaminergic agents modulate fear conditioning in rats

Abstract

The polyamines putrescine, spermine, and spermidine are a group of aliphatic amines that physiologically modulate the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor implicated in memory formation. Given the potential application of these drugs in the treatment of memory disorders, we investigated whether agonists and/or antagonists of the NMDA receptor polyamine binding site alters the memory of fear conditioning and determined the time window in which fear conditioning is modulated by polyaminergic agents given by the systemic route. Post-training intraperitoneal administration of spermidine (10-100 mg/kg) immediately after training increased, whereas arcaine (10 mg/kg) and MK-801 (0.01-0.1 mg/kg) decreased contextual and auditory fear conditioning. Arcaine and MK-801, at doses that had no effect per se, reversed the facilitatory effect of spermidine. Memory of fear conditioning was impaired by polyaminergic blockade up to 180 min but not at 360 min after training. These results provide evidence that systemic administration of polyamine binding site ligands modulate early consolidation of fear conditioning.