Effects of chronic nicotine administration on behavioral parameters and Na⁺/K⁺-ATPase mRNA expression in the brains of male Swiss Albino mice exposed to chronic stress during adolescence

Document Type

Article

Publication Date

Fall 10-27-2025

Abstract

Background

Stress during adolescence leads to the development of major stress-related diseases. The use of psychoactive substances and most psychiatric disorders have been linked to cigarette smoking during adolescence. Na+/K + ATPase isoforms are related to memory formation, stress activity and psychological disorders. Moreover, nicotine downregulates Na+/K + ATPase α2 isoform in rats’ brains. However, its connection to social stress and nicotine addiction is still unclear. Here we aimed for elucidating the effects of nicotine on behavioral parameters and Na+/K + ATPase mRNA in brains of male Swiss Albino mice exposed to chronic stress during adolescence.

Methods

Adolescent male mice were exposed to the sensory contact model (SCM) for 12 days. Nicotine doses (0.1 and 1 mg/kg) were administered intraperitoneally daily for 14 days after SCM. Distance traveled in open field (OF), time spent in open arms in elevated plus maze (EPM), percentage spontaneous alteration in Y-maze and immobility time in forced swimming test (FST) were used to assess locomotor activity, anxiety, spatial memory and depression, respectively. In addition, qRT-PCR was conducted to measure the mRNA levels of Na+ /K + ATPase isoforms in the brain striatum. Group comparisons were analyzed using one-way analysis of variance (ANOVA).

Results

The significantly increased locomotor activity induced by SCM in the aggressive group was significantly reduced by both nicotine treatments. In EPM test, both aggressive and defeated groups showed a significant state of anxiety-like behavior compared to control group which was significantly reduced by 0.1 mg/kg of nicotine. Aggressive and defeated groups showed significant depressive-like response in FST which was almost abolished in defeated group receiving 0.1 mg/kg treatment; however, 1 mg/kg treatment showed the opposite result in the defeated group. SCM significantly increased Na+/K + ATPase-α2 mRNA levels in aggressive and defeated groups compared to control group. In comparison to the control group that received saline, both nicotine treatments significantly increased the levels of Na+/K + ATPase-α2 mRNA in the other two control groups.

Conclusion

This study demonstrates nicotine effects on stress-induced behavioural and molecular alterations in a dose dependent manner. By assessing behavioural outcomes and examining the Na⁺/K⁺ ATPase-α2 expression levels, the study advances understanding of nicotine interactions with chronic stress during adolescence, offering insights into mechanisms underlying nicotine’s behavioral effects.

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