Thiamine Mitigates Nicotine Withdrawal Effects in Adolescent Male Rats: Modulation of Serotonin Metabolism, BDNF, Oxidative Stress, and Neuroinflammation

Abstract

Adolescent nicotine use is particularly concerning due to increased susceptibility to long-term effects and dependence during this critical developmental period. This study investigates the therapeutic effects of thiamine on nicotine withdrawal-induced anxiety, anhedonia, and depression in rats. Adolescent rats received nicotine (2 mg/kg, s.c.) for 21 d, followed by 21 d of withdrawal. Thiamine (25 or 50 mg/kg, i.p.) was administered during exposure and withdrawal. Behavioral assessments were used to evaluate anxiety- and depressive-like symptoms, and biochemical analyses measured oxidative stress markers, serotonin levels, MAO activity, BDNF, and GFAP as indicators of neuroinflammation in the prefrontal cortex. Nicotine withdrawal significantly elevated anxiety-, depression-, and anhedonia-like behaviors, increased oxidative stress, and upregulated MAO-A activity and GFAP expression, indicating neuroinflammatory effects. Notably, thiamine administration during both nicotine exposure and withdrawal effectively alleviated these behavioral impairments, restored serotonin levels, reduced oxidative stress markers, and mitigated the increase in GFAP expression. Additionally, thiamine alone has been shown to alleviate anxiety- and depressive-like behaviors. This study highlights thiamine's potential as a promising intervention for managing psychological distress associated with nicotine withdrawal. Given the high prevalence of adolescent nicotine use and its associated mental health challenges, further research on thiamine's mechanisms and therapeutic potential is warranted to improve treatment strategies during this critical developmental stage.

Keywords: adolescence; anxiety; depression; neuroinflammation; nicotine withdrawal; oxidative stress.

Figure 1.

A detailed timeline outlining the key phases and experimental events in the study. P, postnatal day; OFT, open field test; EPM, elevated plus maze; FST, forced swimming test; SPT, sucrose preference test; MDA, malondialdehyde; TT, total thiol; SOD, superoxide dismutase; CAT, catalase; MAO-A, monoamine oxidase A; BDNF, brain-derived neurotrophic factor; GFAP, glial fibrillary acidic protein.

Figure 2.

Effects of thiamine on anxiety-related behaviors in the open field test (OFT). A, Time spent in the central area of the arena; (B) time spent in the peripheral area. Data are expressed as mean ± SEM (n = 10). Significant differences: *p < 0.05 and ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001 compared with the nicotine–vehicle group.

Figure 3.

Effects of thiamine on anxiety-related behaviors in the elevated plus maze (EPM). A, Time spent in the open arms; (B) time spent in the closed arms. Data are shown as mean ± SEM (n = 10). Significant differences: *p < 0.05 and ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001 compared with the nicotine–vehicle group.

Figure 4.

Effects of thiamine on depressive-like behaviors in the forced swim test. A, Time spent struggling; (B) time spent immobile; (C) time spent swimming. Data are represented as mean ± SEM (n = 10). Significant differences: ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001 compared with the nicotine–vehicle group.

Figure 5.

Effects of thiamine on anhedonia-like behaviors in the sucrose preference test (SPT). Data are shown as mean ± SEM (n = 10). Significant differences: *p < 0.05 and ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.01 and ⁺⁺p < 0.001 compared with the nicotine–vehicle group.

Figure 6.

Effects of thiamine on oxidative stress markers in the prefrontal cortex. A, Malondialdehyde (MDA) levels; (B) total thiol (TT) levels; (C) superoxide dismutase (SOD) activity; (D) catalase (CAT) activity. Data are presented as mean ± SEM (n = 10). Significant differences: *p < 0.05 and ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001 compared with the nicotine–vehicle group.

Figure 7.

Effects of thiamine on cortical levels of neurotransmitters and biomarkers. A, Serotonin levels; (B) monoamine oxidase-A (MAO-A) activity; (C) brain-derived neurotrophic factor (BDNF) levels; (D) glial fibrillary acidic protein (GFAP). Data are expressed as mean ± SEM (n = 10). Significant differences: *p < 0.05 and ***p < 0.001 compared with the vehicle–vehicle group; ⁺p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001 compared with the nicotine–vehicle group.