Introduction: The effects of cytokines on cognitive processes have been extensively studied. Particularly, IL-1beta significantly influences consolidation and persistence of memories that depend on hippocampus. However, the impact of IL-1beta on memory reconsolidation, an important memory process, has not been yet established. A variety of effects of central IL-1beta administration are blocked by the melanocortin alpha-MSH. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, being the MC3R and MC4R predominant in the central nervous system. Therefore, in the present work we studied the effect of IL-1beta on the reconsolidation of a contextual fear memory. We also examined the influence of alpha-MSH and the role of MC4 receptors on the IL-1beta effects on memory reconsolidation.
Materials and methods: Adult male Wistar rats, maintained on controlled conditions, were implanted bilaterally in hippocampus under ketamine -xylazine anesthesia.Each experiment consisted of three phases: conditioning, reactivation session and testing sessions. Training consisted in placing the rat in a chamber with a grid floor attached to a scrambled shocker to provide footshock. Rats were allowed a 3 min acclimation period. After this period, rats received three unsignaled footshocks (0.3mA; 2.5 s). Animals remained in the chamber for additional 2 min and immediately after they were placed in their home cages. Reactivation session: 24hs after training, rats were reexposed to the training context without shocks during 2 min. Test session: Contextual fear conditioning was assessed 24 h after training, by placing the rats in the training environment for a period of 5 min. Memory was assessed and expressed as the percentage of time that rats spent freezing. Different treatments (vehicle, rrIL-1b (R&D Systems), alpha-MSH (Peninsula Laboratories ) and HS024 (selective MC4-R antagonist (NeoMPS) were administered after reactivation.