Polyaminergic agents modulate the reconsolidation of conditioned fear

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Abstract

When consolidated memories are reactivated, they become labile and, to persist, must undergo a new stabilization process called reconsolidation. During reactivation, memory is susceptible to pharmacological interventions that may improve or impair it. Spermidine (SPD) is an endogenous polyamine that physiologically modulates the N-methyl-d-aspartate (NMDA) receptor in mammals by binding on the polyamine-binding site at the NMDA receptor. While polyamine agonists and antagonists of the polyamine binding site on the NMDA receptor respectively improve and impair early consolidation, it has not been defined whether these agents alter memory reconsolidation. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4 mA footshock as unconditioned stimulus. Twenty four hours after training, animals were re-exposed to the apparatus in the absence of shock (reactivation session). Immediately after the reactivation session, SPD (1–30 mg/kg, i.p.) or the antagonist of the polyamine-binding site at the NMDA receptor, arcaine (0.1–10 mg/kg, i.p.), were injected, and the animals were tested in the same apparatus 24 h later. Freezing scores at testing were considered a measure of memory. While SPD (3 and 10 mg/kg) improved, arcaine (1 and 10 mg/kg) impaired memory reconsolidation. These drugs had no effect on memory if they were administered in the absence of reactivation, or 6 h after reactivation session. Arcaine (0.1 mg/kg, i.p.) prevented SPD (3 mg/kg)-induced improvement of memory reconsolidation. Accordingly, SPD (1 mg/kg) prevented arcaine (10 mg/kg)-induced impairment of memory reconsolidation. The amnesic effect of arcaine was not reversed by arcaine administration prior to test, ruling out state dependence in this effect. These results suggest that systemic administration of polyamine binding site ligands modulate memory reconsolidation.

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