Intra-Amygdala Administration of Polyamines Modulates Fear Conditioning in Rats

Abstract

Amygdalar NMDA receptor 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, in the present study we investigated whether the immediate pretraining or post-training bilateral infusion of arcaine, an antagonist of the NMDA receptor polyamine-binding site, 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, whereas spermidine (0.002-20 nmol) increased, contextual and auditory fear conditioning. Arcaine coadministration, 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 or early consolidation (or both) of the fear-conditioning task in the amygdala.

Arcaine and MK-801 make recall state-dependent in rats

“…Accumulating evidence have also suggested that arcaine impairs memory and prevents the promnestic effect of spermidine (Camera et al 2007;Rubin et al 2000Rubin et al , 2001Rubin et al , 2004, a putative positive modulator of the polyamine binding site at the NMDA receptor. Therefore, considering these studies, it is not surprising that arcaine makes the recall of a task statedependent and transfers the response to MK-801, a classic noncompetitive NMDA receptor antagonist.…”

“…Polyamines have also biphasic effects on learning and memory, since they facilitate the acquisition and/or early consolidation of inhibitory avoidance (Berlese et al 2005;Guerra et al 2006;Rubin et al 2000Rubin et al , 2001, fear conditioning (Camera et al 2007;Rubin et al 2004) and the 14-unit Tmaze (Shimada et al 1994) tasks at low doses, but have no effect at high doses. Interestingly, spermidine has no effect on late consolidation and retrieval (Berlese et al 2005).…”

“…Since the facilitatory effects of spermidine on memory are blocked by minute amounts of arcaine, an antagonist of polyamine binding site at the NMDA receptor (Reynolds 1990), the involvement of this receptor in the memory improvement induced by spermidine (Rubin et al 2000(Rubin et al , 2001(Rubin et al , 2004 has been suggested. In line with this view, the noncompetitive NMDAr antagonist, MK-801, reverses the facilitatory effect of spermidine on the memory of fear (Camera et al 2007).…”

“…In line with this view, the noncompetitive NMDAr antagonist, MK-801, reverses the facilitatory effect of spermidine on the memory of fear (Camera et al 2007). Moreover, the administration of arcaine, at doses higher than those required to block the facilitatory effects of spermidine, impairs the memory of inhibitory avoidance and fear conditioning (Rubin et al 2001(Rubin et al , 2004Camera et al 2007) tasks, suggesting the existence of an endogenous "polyaminergic tonus" that might physiologically modulate memory processing.…”

Spermidine-induced improvement of reconsolidation of memory involves calcium-dependent protein kinase in rats

“…In the conditioning trial, each animal was subjected to a single fear conditioning training session, as described by Rubin et al (2004) with some modifications. In brief, the rat was placed in the conditioning chamber (conditioned stimulus, CS) and habituated to the apparatus for 3 min.…”