Addiction & Health

Addiction & Health

Fish Oil Attenuates Nicotine-Seeking Behavior and Oxidative Stress During Withdrawal in Stressed Mice

Articles in Press

Document Type : Original Article

Authors
Mehrdad Shahrani 1, 2
Razieh Mohammadi 3
Maryam Anjomshoa 1
Najmeh Asgharzadeh 2
Fatemeh Azizi 1, 2
1 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
2 Department of Physiology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
3 Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
10.22122/ahj.2026.202157.1770
Abstract
Introduction: Tobacco use remains a major cause of death worldwide, and stress significantly contributes to nicotine addiction and relapse. Emerging evidence indicates that fish oil‑derived omega‑3 fatty acids can reduce cravings and improve mood, offering promise for addiction management. This study examined the effects of fish oil on drug-seeking behavior and anxiety during nicotine withdrawal, particularly under stress.
Methods: Forty male NMRI mice were divided into eight groups based on stress exposure, nicotine or saline, and diet (fish oil or standard). Nicotine (0.5 mg/kg, SC) successfully established conditioned place preference (CPP) without affecting locomotor activity. Drug-seeking behavior was tracked over 8 days across conditioning, addiction, and withdrawal phases. At the end, anxiety levels, serum and brain total antioxidant capacity (TAC), and malondialdehyde (MDA) were quantified.
Results: Fish oil significantly reduced the total time animals remained in the white side during nicotine withdrawal in nicotine-treated groups (P < 0.05), regardless of stress. Notably, this duration increased during withdrawal compared to conditioning (P < 0.05 to P < 0.01). In the open field test, fish oil significantly attenuated anxiety‑like responses (P < 0.001). However, this effect was not observed in the elevated plus maze. Stress-induced MDA levels were significantly decreased by fish oil (P < 0.001).
Conclusion: Fish oil effectively diminishes drug-seeking behavior during nicotine withdrawal and reduces oxidative stress, highlighting its potential as a supportive treatment for nicotine dependence, especially under stress conditions.

Highlights

Fatemeh Azizi(GoogleSholar)(Pubmed)

Keywords
Tobacco use
Stress
Fish oils
Drug-seeking behavior
Oxidative stress
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Addiction & Health

Articles in Press, Accepted Manuscript
Available Online from 27 September 2026