Spermidine prevents the reinstatement of alcohol conditioned place preference

This study investigates whether spermidine (SPD), an endogenous polyamine, alters extinction and reinstatement of alcohol-induced conditioned place preference (CPP) in adult female Swiss mice. CPP was induced by injecting alcohol (1.8 g/kg, i.p.) and placing the animals in the drug-associated compartment for 10 min in four alternate days. During extinction, animals received vehicle or SPD (3, 10 or 30 mg/kg), and were placed in the drug-associated compartment for 10 min in 4 alternate days. Alcohol re-exposure was performed in the alcohol-paired compartment. In a second experiment, after conditioning, animals received vehicle, the N-methyl-d-aspartate (NMDA) receptor polyamine binding site antagonist arcaine (ARC, 0.1 mg/kg), SPD (10 mg/kg) or the association of both (ARC+SDP) in the drug-associated compartment. Animals were then sequentially subjected to alcohol re-exposure and a post-reexposure test. Spermidine did not alter CPP extinction, but prevented the reinstatement of CPP induced by alcohol reexposure. Arcaine prevented the effect of spermidine on alcohol-induced CPP reinstatement. The results suggest that SPD may facilitate the reconsolidation of conditioning memory, disrupting CPP. This effect seems to involve the polyamine binding site at the NMDA receptor, because it is prevented by ARC.