Agmatine Attenuates Behavioral and Biochemical Alterations in Rats Exposed to Ethanol during Adolescence

Background: Ethanol is a psychoactive substance and its use throughout adolescence may have a role in the development of alcoholism in adulthood which causes behavioral changes and structural alterations in particular brain regions that may be the source of these cognitive and motor impairments. As an endogenous amine, agmatine has drawn a lot of interest in relation to drug addiction and its aftereffects. It is an endogenous neuromodulator that has been shown to be a potential agent to manage diverse central nervous system (CNS) disorders. The current investigation aims to elucidate the role of agmatine in mediating behavioral alterations resulting from prolonged exposure to ethanol in rats during their early adolescent years. Methods: Rats received saline (1 ml/kg, p.o.) or ethanol (5 g/kg/day, 35% v/v) once a day from PND 28 to PND 49. Chronic ethanol intoxication during the CNS developing may induce sustainable neurobehavioral alterations in rats. After PND 70, the rats were subjected to behavioural and biochemical tests. Results: Chronic ethanol exposure significantly reduced locomotor activity, increased anxiety-like and depressive behaviors, and impaired cognitive function in adolescent rats. These behavioral alterations were accompanied by elevated oxidative stress, decreased hippocampal BDNF levels, increased levels of proinflammatory cytokines, and disrupted neurotransmitter balance. Agmatine administration at both 40 mg/kg and 80 mg/kg doses notably improved locomotor activity, reduced anxiety and depressive behaviors, and enhanced cognitive performance. Additionally, agmatine treatment reduced oxidative stress, restored BDNF levels, normalized TNF-α and IL6 levels, and corrected the neurotransmitter imbalance in ethanol-exposed rats. Conclusion: Prolonged exposure to ethanol during adolescence elicits persistent behavioural changes, characterized by diminished spontaneous locomotion and impaired balance. Administration of Agmatine effectively restores locomotor activity, alleviates anxiety and depression, and enhances both spatial learning and recognition memory in rats exposed to ethanol. Additionally, agmatine treatment attenuates oxidative stress indicators, including nitrite and lipid peroxidation levels, specifically in the cerebral cortex. These findings suggest that Agmatine holds potential as a viable therapeutic intervention for mitigating both the behavioural and biochemical repercussions induced by ethanol exposure in the rat model.