Ameliorative Effect of Vitamin C Against Tramadol-Induced Learning and Memory Impairment in Juvenile Rat Via Attenuation of Oxidative Stress and Dysfunctional Synaptic Plasticity.

Tramadol (TM) abuse negatively affects the central nervous system, especially brain regions like the hippocampus involved in cognition. Recent studies have demonstrated neuroprotective effects of Vitamin C (Vit C) in various neurological diseases. No study has yet examined the effects of Vit C on tramadol-induced synaptic plasticity impairment. Therefore, we aimed to investigate the neuroprotective effects of Vit C on cognitive performance and synaptic plasticity in tramadol-exposed rats. Fifty-two juvenile male rats (30 days old) were divided into four groups: TM (30 mg/kg/day, intraperitoneally in the first week, 40 mg/kg/day in the second week and 50 mg/kg/day in third and fourth weeks), Vit.C (200 mg/kg/day, orally for 4 weeks), TM + Vit.C (as in the TM and Vit C groups, Vit C administered half an hour prior to TM), and Ctrl (0.25 mL saline/day for 4 weeks). Behavioral tests (open field, Morris water maze, novel object recognition) assessed locomotor activity and memory. In vivo recordings evaluated synaptic plasticity, and hippocampal oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC)] were measured according to the manufacturers' protocols with ELISA. TM caused learning and memory deficits, reduced long-term potentiation (LTP) induction, and disrupted the oxidative stress balance in the hippocampus. In contrast, Vit C inhibited these changes. These findings suggest that Vit C can attenuate cognitive impairments associated with chronic TM consumption, likely through modulation of hippocampal oxidative stress and enhancement of LTP induction. Therefore, Vit C could be a promising candidate for further investigation as a potential therapeutic agent to mitigate cognitive dysfunction associated with TM use.