Antidepressants modulate behavioral, biochemical, and histological alterations induced by chronic aluminum chloride administration in wistar rats

Objective: To assess the effect of duloxetine and escitalopram on aluminum chloride (AlCl3)-induced memory impairment in rats. Materials and Methods: Thirty rats were used. Group-I (control) and Group-II (toxic control) received 2% gum acacia, 10 mL/kg and AlCl₃, 175 mg/kg, respectively. Group-III (standard), Group-IV, and Group-V (test drug groups) received rivastigmine (1 mg/kg), duloxetine (10 mg/kg), and escitalopram (10 mg/kg), respectively, along with AlCl₃, 175 mg/kg. All drugs and AlCl₃ were administered orally daily for 2 months. The effect on cognition was assessed by Morris water maze (MWM). Brain acetylcholinesterase levels, oxidative stress parameters, and histology of the hippocampus were also evaluated. Results: Rats treated with only AlCl₃ showed significant (P < 0.001) increase in latency during acquisition trials of day-3 and day-4 and decrease in percentage of both time spent and distance traveled in target zone during probe trial in MWM. Malondialdehyde was increased and glutathione decreased in the brain. Histopathology of the hippocampus showed unhealthy cellular architecture with a large number of degenerated cells. All these changes were significantly reversed in rivastigmine and test drug groups. Chronic administration of AlCl₃ resulted in lowering of brain cholinesterase levels (P < 0.001) versus control. Cholinesterase levels were further significantly (P < 0.05) lowered in rats who received AlCl₃ along with either rivastigmine or escitalopram. Conclusion: Escitalopram and duloxetine exerted a protective effect against AlCl₃-induced memory impairment in rats.