Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice.

Autor: Aomine Y; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Research Fellow of Japan Society for the Promotion of Science, Suita, Japan., Shimo Y; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan., Sakurai K; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.; Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, Suita, Osaka, Japan., Abe M; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan., Macpherson T; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan., Ozawa T; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan., Hikida T; Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2025 Jan; Vol. 169 (1), pp. e16227. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1111/jnc.16227
Abstrakt: Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine intraperitoneal (i.p.) administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, 0.5 mg/kg nicotine significantly improved performance in the VDR, but not the VD, task, while 0.5 mg/kg nicotine significantly worsened performance in the VD, but not VDR task in female mice. Furthermore, 0.25 mg/kg nicotine significantly worsened performance in the VD and VDR task only in female mice. Next, to investigate the cellular mechanisms that underlie the sex difference in the effects of nicotine on cognition, transcriptomic analyses were performed focusing on the medial prefrontal cortex tissue samples from male and female mice that had received continuous administration of nicotine for 3 or 18 days. As a result of pathway enrichment analysis and protein-protein interaction analysis using gene sets of differentially expressed genes, decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility. Our result suggests that nicotine modulates cognitive function in a sex-dependent manner by alternating the expression of specific gene sets in the medial prefrontal cortex.
(© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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