Dose dependent behavioral effects of agmatine in rats

Agmatine, a decarboxylated metabolite of L -arginine, exhibits neuroprotective, antidepressant, and anxiolytic properties through its modulation of NMDA receptors, monoamine pathways, and antioxidant defenses. Although its therapeutic potential is well recognized, its dose-dependent behavioral and biochemical effects remain insufficiently characterized. This study investigated the chronic, dose-dependent effects of agmatine on locomotor activity, anxiety-like and depressive-like behaviors, cognitive performance, and oxidative stress markers in rats. albino Wistar rats (n = 24) received oral agmatine at 50, 100, or 200 mg/kg for 28 days, while controls received water. Behavioral assessments included the open field test, forced swim test, elevated plus maze, light/dark transition test, and Morri’s water maze. Oxidative stress markers (MDA, SOD, CAT, GSH, GPx) were quantified from brain homogenates. Statistical analysis was performed using one-way ANOVA (p < 0.05). Agmatine produced significant dose-dependent improvements in locomotion and exploration, with the most pronounced effects at 100 and 200 mg/kg. Antidepressant-like behavior was evident through increased struggling in the forced swim test (p < 0.01), while anxiolytic effects were observed across all doses in both the elevated plus maze and light/dark transition tasks (p < 0.01). Cognitive function improved significantly, as shown by reduced escape latencies during training, acquisition, and retention phases of the Morris water maze (p < 0.01). Biochemically, agmatine reduced lipid peroxidation and elevated enzymatic antioxidant activity in a dose-dependent manner. 100 mg/kg dose consistently produce the strongest behavioral and antioxidant responses. Chronic agmatine administration exerts robust dose-dependent behavioral and neuroprotective effects, with 100 mg/kg identified as the optimal effective dose. These findings support agmatine as a safe candidate for therapeutic applications targeting anxiety, depression, cognitive impairment, and oxidative stress. • Chronic agmatine administration produced clear dose-dependent behavioral improvements in rats. • Agmatine enhanced locomotor activity, reduced depressive-like behavior, and produced strong anxiolytic effects. • Spatial learning and memory significantly improved in a dose-dependent manner in the Morris water maze. • Agmatine reduced lipid peroxidation and increased endogenous antioxidant enzyme activity (SOD, CAT, GSH, GPx). • The 100 mg/kg dose consistently produced the most robust behavioral and antioxidant effects without toxicity.