Nicotine-induced enhancement of recognition memory through conserved neuronal development networks in rat and human experimental models

Objectives This study aims to identify molecular mechanisms underlying nicotine-induced memory enhancement across both rodent and human neuronal models, with the goal of informing the development of alternative therapeutic strategies for memory-related disorders. Methods Fischer 344 rats received nicotine (0.25 mg/kg s.c. twice daily, 17 days) or saline, followed by Novel Object Recognition Test (NORT) assessment. Transcriptomic data from nicotine-exposed F344 rat hippocampus (GSE47474) and human SH-SY5Y cells (1 h or 24 h nicotine, GSE11208) were analyzed using Ingenuity Pathway Analysis (IPA) to identify enriched canonical pathways, upstream regulators, and diseases and biological functions. Results Nicotine-treated F344 rats demonstrated enhanced recognition memory following the NORT assessment. Transcriptomic analysis revealed 69 differentially expressed molecules contributing to the Memory function network. Cross-species analysis revealed conserved IPA-predicted activation or inhibition of canonical pathways such as GABAergic receptor signaling, upstream regulators such as NTRK2, and biological functions such as Neuritogenesis. Conclusions Our findings provide insight into the molecular networks associated with nicotine-induced memory enhancement and identify candidate pathways, particularly NTRK2-mediated signaling, that warrant further investigation as potential therapeutic targets for memory-related disorders.