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<p>Anxiety and depression are prevalent mental health disorders that often accompany substance withdrawal, underscoring the need for effective therapeutic interventions. This study investigates the potential of pyridoxine to alleviate nicotine withdrawal–induced anxiety and depression by enhancing serotonin metabolism and modulating oxidative stress pathways. Male adolescent rats were administered nicotine (2&#xa0;mg/kg, s.c.) daily for 21&#xa0;days, followed by a 21-day withdrawal period. Pyridoxine was administered throughout both the exposure and withdrawal phases. Behavioral evaluations including open field test, elevated plus maze, forced swimming test, and sucrose preference test were performed to assess anxiety and depression-like behaviors. Additionally, biochemical analyses of the prefrontal cortex were conducted to quantify serotonin metabolism and key markers of oxidative stress. Nicotine withdrawal induced pronounced anxiety and depression-like behaviors in adolescent rats, which were associated with disrupted serotonin metabolism and increased oxidative stress in the prefrontal cortex. Pyridoxine treatment effectively mitigated these alterations by modulating serotonin turnover and reducing oxidative stress, highlighting its potential neuroprotective role during withdrawal. The findings of this study demonstrate that pyridoxine exerts significant anxiolytic and antidepressant-like effects during nicotine withdrawal, likely through the restoration of serotonin metabolism and attenuation of oxidative stress in the prefrontal cortex. Pyridoxine may therefore represent a promising adjunctive strategy for managing nicotine withdrawal–related neuropsychiatric symptoms, particularly in adolescent populations.</p>

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Pyridoxine attenuates nicotine withdrawal–associated anxiety and depression in male rats through serotonin regulation and oxidative stress reduction

  • 期刊论文

  • 发表日期：

    2025年7月30日

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  • Murtaza Haidary,
  • Elham Akbari,
  • Dawood Hossaini,
  • Mustafa Ansari,
  • Hossain Rezayee,
  • Adamkhan Alipour,
  • Meysam Sajjadi

摘要

Anxiety and depression are prevalent mental health disorders that often accompany substance withdrawal, underscoring the need for effective therapeutic interventions. This study investigates the potential of pyridoxine to alleviate nicotine withdrawal–induced anxiety and depression by enhancing serotonin metabolism and modulating oxidative stress pathways. Male adolescent rats were administered nicotine (2 mg/kg, s.c.) daily for 21 days, followed by a 21-day withdrawal period. Pyridoxine was administered throughout both the exposure and withdrawal phases. Behavioral evaluations including open field test, elevated plus maze, forced swimming test, and sucrose preference test were performed to assess anxiety and depression-like behaviors. Additionally, biochemical analyses of the prefrontal cortex were conducted to quantify serotonin metabolism and key markers of oxidative stress. Nicotine withdrawal induced pronounced anxiety and depression-like behaviors in adolescent rats, which were associated with disrupted serotonin metabolism and increased oxidative stress in the prefrontal cortex. Pyridoxine treatment effectively mitigated these alterations by modulating serotonin turnover and reducing oxidative stress, highlighting its potential neuroprotective role during withdrawal. The findings of this study demonstrate that pyridoxine exerts significant anxiolytic and antidepressant-like effects during nicotine withdrawal, likely through the restoration of serotonin metabolism and attenuation of oxidative stress in the prefrontal cortex. Pyridoxine may therefore represent a promising adjunctive strategy for managing nicotine withdrawal–related neuropsychiatric symptoms, particularly in adolescent populations.