Poliaminas modulam a memória nas tarefas de medo condicionado e esquiva inibitória em ratos

Abstract

The polyamines, spermine, spermidine and putrescine, are a group of aliphatic amines that interact with diverse cellular targets such as nucleic acids and proteins. The polyamines may act as physiological modulators of N-methyl-D-aspartate (NMDA) receptors. The processes mediated by NMDA receptor include synaptic plasticity and formation of neural circuitry. Amygdalar NMDA receptors activation has been implicated in the acquisition of fear memories in rats. However, little is known about the role of endogenous modulators of the NMDA receptor, such as polyamines, in Pavlovian fear conditioning learning. Therefore, the present study was conducted to investigate whether the immediate pre-training or post-training bilateral infusion of arcaine, an antagonist of the NMDA receptor polyamine binding site, and/or spermidine, an agonist of the NMDA receptor polyamine binding site, into the amygdala affected classical fear conditioning in rats. Bilateral microinjections of arcaine (0,0002-0,2 nmol) decreased, while spermidine (0,002-20 nmol) increased contextual and auditory fear conditioning. Arcaine co-administration, at a dose that had no effect per se, reversed the facilitatory effect of spermidine.These results provide evidence that endogenous and exogenous polyamines modulate the acquisition and/or early consolidation of the fear conditioning task in the amygdala. Little is known thus far about the period of time during which memory processing in the hippocampus is sensitive to polyamines, and whether polyamines affect memory retrieval. The present study valued the effect of bilateral infusions of spermidine (0,02-2 nmol), a polyamine agonist, into the CA1 region of the rat dorsal hippocampus on inhibitory avoidance learning 30 minutes pre-training, immediately post-training, 6 hours post-training or 10 minutes pre-test. Bilateral microinjections of 0,2 nmol spermidine prolonged step-down latencies compared to the respective control group when administered 30 minutes pre-training or immediately post-training. These results provide evidence that the modulatory effects of spermidine on the acquisition and/or early consolidation of memory of inhibitory avoidance tasks in the hippocampus occur within a limited time window.