Systemic administration of polyaminergic agents modulate fear conditioning in rats

Abstract

These results provide evidence that systemic administration of polyamine binding site ligands modulate early consolidation of fear conditioning.

Differential effects of histamine H3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice

“…By contrast, in Experiments 3 and 6 thioperamide readily abolished the disruption of both consolidation and reconsolidation induced by a representative dose of the non-competitive NMDA antagonist dizocilpine. The disruptive effects of dizocilpine per se were characterized prior to these experiments (Experiments 2 and 5), replicating and complementing previous comparable results obtained in rats and mice tested for contextual fear memories (Suzuki et al, 2004;Lee et al, 2006;Camera et al, 2007). Note that the dizocilpine effects on reconsolidation were specific since no effect at all was obtained when the drug was given outside of the test context.…”

“…The establishment of such a memory, which depends on the integrity of the amygdaloid-hippocampal complex (Kim and Jung, 2006), relies on the pairing of a footshock (the unconditioned stimulus; US) with a circumscribed context that subsequently becomes a conditional stimulus (CS) eliciting on its own conditioned freezing (CR), the natural response to the initial foot-shock (UR) in rodents. As for many learning-and-memory procedures, both consolidation and reconsolidation of contextual fear memories can readily be disrupted or facilitated by systemic injections of NMDA antagonists or the partial NMDA agonist D-cycloserine, respectively (Suzuki et al, 2004;Lee et al, 2006;Camera et al, 2007). Since histamine H 3 inverse agonists can prevent the disruptive effects that NMDA receptor antagonists exert on consolidation of several cognitive tasks, as seen above, we also examined the interactive effects of thioperamide and the representative non-competitive NMDA antagonist dizocilpine (MK-801) on reconsolidation.…”

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

“…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.…”

“…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).…”

The histamine H3-receptor inverse agonist Pitolisant improves fear memory in mice

“…During the consolidation phase, memories are susceptible to disruption when amnesic treatments are applied shortly after learning such as electroconvulsive shocks [13]. Glutamate transmission and in particular N-methyld-aspartate (NMDA) receptors play a critical role in consolidation of fear memories since the blockade of NMDA receptors impairs memory consolidation [14] whereas NMDA receptor activation facilitates consolidation [15]. In addition, other neurotransmitter systems like histamine can facilitate the consolidation of memories [16].…”