Spermidine improves memory consolidation in a contextual fear conditioning task in adult zebrafish

Memory is essential for survival, depending on the activation of neurotransmitter signaling pathways, such as the glutamatergic system. Polyamines are endogenous amines that can be released from presynaptic neurons and stimulate glutamatergic N-methyl-d-aspartate (NMDA) receptors. Although polyamines are known to influence cognitive processes, the potential modulatory role of spermidine (SPD) in memory consolidation of zebrafish has never been explored yet. Here, we aimed to evaluate the influence of SPD on memory consolidation of adult zebrafish using a contextual fear conditioning protocol. On day 1, fish were conditioned to an aversive naturalistic stimulus (conspecific alarm substance - CAS) as unconditioned stimulus (US) or exposed to dechlorinated water (control) in a tank with visual cues (conditioned stimulus, CS) for 5 min. Immediately after the training session, fish were randomly selected from each group and divided into different subgroups. A set of animals was intraperitoneally injected with saline (SAL) or SPD (1 or 10 mg/kg), while another cohort of non-injected fish was tested to analyze the exacerbation of CS-CAS responses 24 h later. On day 2 (test session), animals were reintroduced into the same contextual CS filled with dechlorinated water. We found that the US used elicited a robust fear recall on the test session, while SPD alone did not affect zebrafish behaviors. Conversely, 10 mg/kg SPD facilitated memory consolidation by increasing CAS-induced fear conditioning responses, without affecting locomotion. Overall, our findings support that SPD increases fear conditioning responses in zebrafish, suggesting a conserved role of polyamines in learning and memory processes.